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39 60 peptide binding‐motif structure_element Structure‐activity relationship of the peptide binding‐motif mediating the BRCA2:RAD51 protein–protein interaction TITLE
75 86 BRCA2:RAD51 complex_assembly Structure‐activity relationship of the peptide binding‐motif mediating the BRCA2:RAD51 protein–protein interaction TITLE
1 6 RAD51 protein RAD51 is a recombinase involved in the homologous recombination of double‐strand breaks in DNA. ABSTRACT
12 23 recombinase protein_type RAD51 is a recombinase involved in the homologous recombination of double‐strand breaks in DNA. ABSTRACT
0 5 RAD51 protein RAD51 forms oligomers by binding to another molecule of RAD51 via an ‘FxxA’ motif, and the same recognition sequence is similarly utilised to bind BRCA2. ABSTRACT
12 21 oligomers oligomeric_state RAD51 forms oligomers by binding to another molecule of RAD51 via an ‘FxxA’ motif, and the same recognition sequence is similarly utilised to bind BRCA2. ABSTRACT
56 61 RAD51 protein RAD51 forms oligomers by binding to another molecule of RAD51 via an ‘FxxA’ motif, and the same recognition sequence is similarly utilised to bind BRCA2. ABSTRACT
70 74 FxxA structure_element RAD51 forms oligomers by binding to another molecule of RAD51 via an ‘FxxA’ motif, and the same recognition sequence is similarly utilised to bind BRCA2. ABSTRACT
147 152 BRCA2 protein RAD51 forms oligomers by binding to another molecule of RAD51 via an ‘FxxA’ motif, and the same recognition sequence is similarly utilised to bind BRCA2. ABSTRACT
33 41 mutation experimental_method We have tabulated the effects of mutation of this sequence, across a variety of experimental methods and from relevant mutations observed in the clinic. ABSTRACT
7 14 mutants protein_state We use mutants of a tetrapeptide sequence to probe the binding interaction, using both isothermal titration calorimetry and X‐ray crystallography. ABSTRACT
20 32 tetrapeptide chemical We use mutants of a tetrapeptide sequence to probe the binding interaction, using both isothermal titration calorimetry and X‐ray crystallography. ABSTRACT
87 119 isothermal titration calorimetry experimental_method We use mutants of a tetrapeptide sequence to probe the binding interaction, using both isothermal titration calorimetry and X‐ray crystallography. ABSTRACT
124 145 X‐ray crystallography experimental_method We use mutants of a tetrapeptide sequence to probe the binding interaction, using both isothermal titration calorimetry and X‐ray crystallography. ABSTRACT
39 68 tetrapeptide mutational study experimental_method Where possible, comparison between our tetrapeptide mutational study and the previously reported mutations is made, discrepancies are discussed and the importance of secondary structure in interpreting alanine scanning and mutational data of this nature is considered. ABSTRACT
202 218 alanine scanning experimental_method Where possible, comparison between our tetrapeptide mutational study and the previously reported mutations is made, discrepancies are discussed and the importance of secondary structure in interpreting alanine scanning and mutational data of this nature is considered. ABSTRACT
0 10 Eukaryotic taxonomy_domain Eukaryotic RAD51, archeal RadA and prokaryotic RecA are a family of ATP‐dependent recombinases involved in homologous recombination (HR) of double‐strand breaks in DNA 1. ABBR
11 16 RAD51 protein Eukaryotic RAD51, archeal RadA and prokaryotic RecA are a family of ATP‐dependent recombinases involved in homologous recombination (HR) of double‐strand breaks in DNA 1. ABBR
18 25 archeal taxonomy_domain Eukaryotic RAD51, archeal RadA and prokaryotic RecA are a family of ATP‐dependent recombinases involved in homologous recombination (HR) of double‐strand breaks in DNA 1. ABBR
26 30 RadA protein Eukaryotic RAD51, archeal RadA and prokaryotic RecA are a family of ATP‐dependent recombinases involved in homologous recombination (HR) of double‐strand breaks in DNA 1. ABBR
35 46 prokaryotic taxonomy_domain Eukaryotic RAD51, archeal RadA and prokaryotic RecA are a family of ATP‐dependent recombinases involved in homologous recombination (HR) of double‐strand breaks in DNA 1. ABBR
47 51 RecA protein Eukaryotic RAD51, archeal RadA and prokaryotic RecA are a family of ATP‐dependent recombinases involved in homologous recombination (HR) of double‐strand breaks in DNA 1. ABBR
68 94 ATP‐dependent recombinases protein_type Eukaryotic RAD51, archeal RadA and prokaryotic RecA are a family of ATP‐dependent recombinases involved in homologous recombination (HR) of double‐strand breaks in DNA 1. ABBR
0 5 RAD51 protein RAD51 interacts with BRCA2, and is thought to localise RAD51 to sites of DNA damage 2, 3. ABBR
21 26 BRCA2 protein RAD51 interacts with BRCA2, and is thought to localise RAD51 to sites of DNA damage 2, 3. ABBR
55 60 RAD51 protein RAD51 interacts with BRCA2, and is thought to localise RAD51 to sites of DNA damage 2, 3. ABBR
5 10 BRCA2 protein Both BRCA2 and RAD51 together are vital for helping to repair and maintain a high fidelity in DNA replication. ABBR
15 20 RAD51 protein Both BRCA2 and RAD51 together are vital for helping to repair and maintain a high fidelity in DNA replication. ABBR
0 5 BRCA2 protein BRCA2 especially has garnered much attention in a clinical context, as many mutations have been identified that drive an increased risk of cancer in individuals 4, 5. ABBR
33 44 BRCA2:RAD51 complex_assembly Although the inactivation of the BRCA2:RAD51 DNA repair pathway can cause genomic instability and eventual tumour development, an inability to repair breaks in DNA may also engender a sensitivity to ionising radiation 6, 7. ABBR
71 82 BRCA2:RAD51 complex_assembly For this reason it is hypothesised that in tumour cells with an intact BRCA2:RAD51 repair pathway, small molecules which prevent the interaction between RAD51 and BRCA2 may confer radiosensitivity by disabling the HR pathway 8. ABBR
153 158 RAD51 protein For this reason it is hypothesised that in tumour cells with an intact BRCA2:RAD51 repair pathway, small molecules which prevent the interaction between RAD51 and BRCA2 may confer radiosensitivity by disabling the HR pathway 8. ABBR
163 168 BRCA2 protein For this reason it is hypothesised that in tumour cells with an intact BRCA2:RAD51 repair pathway, small molecules which prevent the interaction between RAD51 and BRCA2 may confer radiosensitivity by disabling the HR pathway 8. ABBR
62 73 BRC repeats structure_element The interaction between the two proteins is mediated by eight BRC repeats, which are characterised by a conserved ‘FxxA’ motif 9. ABBR
104 113 conserved protein_state The interaction between the two proteins is mediated by eight BRC repeats, which are characterised by a conserved ‘FxxA’ motif 9. ABBR
114 128 ‘FxxA’ motif 9 structure_element The interaction between the two proteins is mediated by eight BRC repeats, which are characterised by a conserved ‘FxxA’ motif 9. ABBR
0 5 RAD51 protein RAD51 and RadA proteins also contain an ‘FxxA’ sequence (FTTA for human RAD51) through which it can bind to other RAD51 and RadA molecules, and oligomerise to form higher order filament structures on DNA. ABBR
10 14 RadA protein RAD51 and RadA proteins also contain an ‘FxxA’ sequence (FTTA for human RAD51) through which it can bind to other RAD51 and RadA molecules, and oligomerise to form higher order filament structures on DNA. ABBR
41 45 FxxA structure_element RAD51 and RadA proteins also contain an ‘FxxA’ sequence (FTTA for human RAD51) through which it can bind to other RAD51 and RadA molecules, and oligomerise to form higher order filament structures on DNA. ABBR
57 61 FTTA structure_element RAD51 and RadA proteins also contain an ‘FxxA’ sequence (FTTA for human RAD51) through which it can bind to other RAD51 and RadA molecules, and oligomerise to form higher order filament structures on DNA. ABBR
66 71 human species RAD51 and RadA proteins also contain an ‘FxxA’ sequence (FTTA for human RAD51) through which it can bind to other RAD51 and RadA molecules, and oligomerise to form higher order filament structures on DNA. ABBR
72 77 RAD51 protein RAD51 and RadA proteins also contain an ‘FxxA’ sequence (FTTA for human RAD51) through which it can bind to other RAD51 and RadA molecules, and oligomerise to form higher order filament structures on DNA. ABBR
114 119 RAD51 protein RAD51 and RadA proteins also contain an ‘FxxA’ sequence (FTTA for human RAD51) through which it can bind to other RAD51 and RadA molecules, and oligomerise to form higher order filament structures on DNA. ABBR
124 128 RadA protein RAD51 and RadA proteins also contain an ‘FxxA’ sequence (FTTA for human RAD51) through which it can bind to other RAD51 and RadA molecules, and oligomerise to form higher order filament structures on DNA. ABBR
11 15 FxxA structure_element The common FxxA motifs of both the BRC repeats and RAD51 oligomerisation sequence are recognised by the same FxxA‐binding site of RAD51. ABBR
35 46 BRC repeats structure_element The common FxxA motifs of both the BRC repeats and RAD51 oligomerisation sequence are recognised by the same FxxA‐binding site of RAD51. ABBR
51 56 RAD51 protein The common FxxA motifs of both the BRC repeats and RAD51 oligomerisation sequence are recognised by the same FxxA‐binding site of RAD51. ABBR
57 81 oligomerisation sequence structure_element The common FxxA motifs of both the BRC repeats and RAD51 oligomerisation sequence are recognised by the same FxxA‐binding site of RAD51. ABBR
109 126 FxxA‐binding site site The common FxxA motifs of both the BRC repeats and RAD51 oligomerisation sequence are recognised by the same FxxA‐binding site of RAD51. ABBR
130 135 RAD51 protein The common FxxA motifs of both the BRC repeats and RAD51 oligomerisation sequence are recognised by the same FxxA‐binding site of RAD51. ABBR
73 87 binding energy evidence In general, the dominant contribution of certain residues to the overall binding energy of a protein–protein interaction are known as ‘hot‐spot’ residues. ABBR
135 143 hot‐spot site In general, the dominant contribution of certain residues to the overall binding energy of a protein–protein interaction are known as ‘hot‐spot’ residues. ABBR
84 91 pockets site Interestingly, small molecule inhibitors of PPIs are often found to occupy the same pockets which are otherwise occupied by hot‐spot residues in the native complex. ABBR
124 132 hot‐spot site Interestingly, small molecule inhibitors of PPIs are often found to occupy the same pockets which are otherwise occupied by hot‐spot residues in the native complex. ABBR
149 155 native protein_state Interestingly, small molecule inhibitors of PPIs are often found to occupy the same pockets which are otherwise occupied by hot‐spot residues in the native complex. ABBR
46 55 hot‐spots site It is therefore of great interest to identify hot‐spots in an effort to guide drug discovery efforts against a PPI. ABBR
49 67 strongly conserved protein_state Further, a correlation between residues that are strongly conserved and hot‐spot residues has been reported 10. ABBR
72 80 hot‐spot site Further, a correlation between residues that are strongly conserved and hot‐spot residues has been reported 10. ABBR
84 97 phenylalanine residue_name Purely based on the amino acid consensus sequence reported by Pellegrini et al., 11 phenylalanine and alanine would both be expected to be hot‐spots and to a lesser extent, threonine. ABBR
102 109 alanine residue_name Purely based on the amino acid consensus sequence reported by Pellegrini et al., 11 phenylalanine and alanine would both be expected to be hot‐spots and to a lesser extent, threonine. ABBR
139 148 hot‐spots site Purely based on the amino acid consensus sequence reported by Pellegrini et al., 11 phenylalanine and alanine would both be expected to be hot‐spots and to a lesser extent, threonine. ABBR
173 182 threonine residue_name Purely based on the amino acid consensus sequence reported by Pellegrini et al., 11 phenylalanine and alanine would both be expected to be hot‐spots and to a lesser extent, threonine. ABBR
38 54 highly conserved protein_state However, whilst the identification of highly conserved residues may be a good starting point for identifying hot‐spots, experimental validation by mutation of these sequences is vital. ABBR
109 118 hot‐spots site However, whilst the identification of highly conserved residues may be a good starting point for identifying hot‐spots, experimental validation by mutation of these sequences is vital. ABBR
147 155 mutation experimental_method However, whilst the identification of highly conserved residues may be a good starting point for identifying hot‐spots, experimental validation by mutation of these sequences is vital. ABBR
34 38 FxxA structure_element The importance of residues in the FxxA motif has been probed by a variety of techniques, collated in Table 1. ABBR
9 17 mutating experimental_method Briefly, mutating phenylalanine to glutamic acid inactivated the BRC4 peptide and prevented RAD51 oligomerisation 11, 12. ABBR
18 31 phenylalanine residue_name Briefly, mutating phenylalanine to glutamic acid inactivated the BRC4 peptide and prevented RAD51 oligomerisation 11, 12. ABBR
35 48 glutamic acid residue_name Briefly, mutating phenylalanine to glutamic acid inactivated the BRC4 peptide and prevented RAD51 oligomerisation 11, 12. ABBR
49 60 inactivated protein_state Briefly, mutating phenylalanine to glutamic acid inactivated the BRC4 peptide and prevented RAD51 oligomerisation 11, 12. ABBR
65 69 BRC4 chemical Briefly, mutating phenylalanine to glutamic acid inactivated the BRC4 peptide and prevented RAD51 oligomerisation 11, 12. ABBR
92 97 RAD51 protein Briefly, mutating phenylalanine to glutamic acid inactivated the BRC4 peptide and prevented RAD51 oligomerisation 11, 12. ABBR
2 25 phenylalanine‐truncated protein_state A phenylalanine‐truncated BRC4 is also found to be inactive 13, however, introducing a tryptophan for phenylalanine was found to have no significant effect on BRC4 affinity 12. ABBR
26 30 BRC4 chemical A phenylalanine‐truncated BRC4 is also found to be inactive 13, however, introducing a tryptophan for phenylalanine was found to have no significant effect on BRC4 affinity 12. ABBR
51 59 inactive protein_state A phenylalanine‐truncated BRC4 is also found to be inactive 13, however, introducing a tryptophan for phenylalanine was found to have no significant effect on BRC4 affinity 12. ABBR
73 84 introducing experimental_method A phenylalanine‐truncated BRC4 is also found to be inactive 13, however, introducing a tryptophan for phenylalanine was found to have no significant effect on BRC4 affinity 12. ABBR
87 97 tryptophan residue_name A phenylalanine‐truncated BRC4 is also found to be inactive 13, however, introducing a tryptophan for phenylalanine was found to have no significant effect on BRC4 affinity 12. ABBR
102 115 phenylalanine residue_name A phenylalanine‐truncated BRC4 is also found to be inactive 13, however, introducing a tryptophan for phenylalanine was found to have no significant effect on BRC4 affinity 12. ABBR
159 163 BRC4 chemical A phenylalanine‐truncated BRC4 is also found to be inactive 13, however, introducing a tryptophan for phenylalanine was found to have no significant effect on BRC4 affinity 12. ABBR
164 172 affinity evidence A phenylalanine‐truncated BRC4 is also found to be inactive 13, however, introducing a tryptophan for phenylalanine was found to have no significant effect on BRC4 affinity 12. ABBR
2 11 glutamine residue_name A glutamine replacing the histidine in BRC4 maintains BRC4 activity 13. ABBR
12 21 replacing experimental_method A glutamine replacing the histidine in BRC4 maintains BRC4 activity 13. ABBR
26 35 histidine residue_name A glutamine replacing the histidine in BRC4 maintains BRC4 activity 13. ABBR
39 43 BRC4 chemical A glutamine replacing the histidine in BRC4 maintains BRC4 activity 13. ABBR
54 58 BRC4 chemical A glutamine replacing the histidine in BRC4 maintains BRC4 activity 13. ABBR
15 19 BRC3 chemical The ability of BRC3 to interact with RAD51 nucleoprotein filaments is disrupted when threonine is mutated to an alanine 3. ABBR
37 42 RAD51 protein The ability of BRC3 to interact with RAD51 nucleoprotein filaments is disrupted when threonine is mutated to an alanine 3. ABBR
85 94 threonine residue_name The ability of BRC3 to interact with RAD51 nucleoprotein filaments is disrupted when threonine is mutated to an alanine 3. ABBR
98 105 mutated experimental_method The ability of BRC3 to interact with RAD51 nucleoprotein filaments is disrupted when threonine is mutated to an alanine 3. ABBR
112 119 alanine residue_name The ability of BRC3 to interact with RAD51 nucleoprotein filaments is disrupted when threonine is mutated to an alanine 3. ABBR
11 19 mutating experimental_method Similarly, mutating alanine to glutamic acid in the RAD51 oligomerisation sequence 11 or to serine in BRC4 13 leads to loss of interaction in both cases. ABBR
20 27 alanine residue_name Similarly, mutating alanine to glutamic acid in the RAD51 oligomerisation sequence 11 or to serine in BRC4 13 leads to loss of interaction in both cases. ABBR
31 44 glutamic acid residue_name Similarly, mutating alanine to glutamic acid in the RAD51 oligomerisation sequence 11 or to serine in BRC4 13 leads to loss of interaction in both cases. ABBR
52 57 RAD51 protein Similarly, mutating alanine to glutamic acid in the RAD51 oligomerisation sequence 11 or to serine in BRC4 13 leads to loss of interaction in both cases. ABBR
58 82 oligomerisation sequence structure_element Similarly, mutating alanine to glutamic acid in the RAD51 oligomerisation sequence 11 or to serine in BRC4 13 leads to loss of interaction in both cases. ABBR
92 98 serine residue_name Similarly, mutating alanine to glutamic acid in the RAD51 oligomerisation sequence 11 or to serine in BRC4 13 leads to loss of interaction in both cases. ABBR
102 106 BRC4 chemical Similarly, mutating alanine to glutamic acid in the RAD51 oligomerisation sequence 11 or to serine in BRC4 13 leads to loss of interaction in both cases. ABBR
4 8 BRC5 chemical The BRC5 repeat in humans has serine in the place of alanine, and is thought to be a nonbinding repeat 12. ABBR
19 25 humans species The BRC5 repeat in humans has serine in the place of alanine, and is thought to be a nonbinding repeat 12. ABBR
30 36 serine residue_name The BRC5 repeat in humans has serine in the place of alanine, and is thought to be a nonbinding repeat 12. ABBR
53 60 alanine residue_name The BRC5 repeat in humans has serine in the place of alanine, and is thought to be a nonbinding repeat 12. ABBR
85 102 nonbinding repeat structure_element The BRC5 repeat in humans has serine in the place of alanine, and is thought to be a nonbinding repeat 12. ABBR
43 47 FxxA structure_element Mutations identified in the clinic, in the FxxA region of the BRC repeats of BRCA2 are collated in Table 1 14. ABBR
62 73 BRC repeats structure_element Mutations identified in the clinic, in the FxxA region of the BRC repeats of BRCA2 are collated in Table 1 14. ABBR
77 82 BRCA2 protein Mutations identified in the clinic, in the FxxA region of the BRC repeats of BRCA2 are collated in Table 1 14. ABBR
163 168 RAD51 protein For completeness, we present them here with this caveat, and to make the comment that these clinical mutations are consistent with abrogating the interaction with RAD51. ABBR
11 15 FxxA structure_element Summary of FxxA‐relevant mutations previously reported and degree of characterisation. TABLE
50 54 FxxA structure_element The mutation, relevant peptide context, resulting FxxA motif sequence and experimental technique for each entry is given. TABLE
27 31 FxxA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
62 67 RAD51 protein "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
69 73 FTTA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
75 79 F86E mutant "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
80 84 ETTA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
85 104 Immunoprecipitation experimental_method "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
121 125 BRC4 chemical "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
127 131 FHTA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
133 139 F1524E mutant "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
140 144 EHTA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
145 162 Competitive ELISA experimental_method "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
174 182 inactive protein_state "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
185 189 BRC4 chemical "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
191 195 FHTA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
197 203 F1524W mutant "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
204 208 WHTA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
209 226 Competitive ELISA experimental_method "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
253 255 WT protein_state "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
258 262 BRC4 chemical "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
264 268 FHTA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
270 276 F1524V mutant "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
277 281 VHTA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
282 287 BRCA2 protein "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
314 318 BRC4 chemical "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
320 324 FHTA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
326 332 ΔF1524 mutant "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
334 337 HTA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
354 363 RAD51‐DNA complex_assembly "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
383 391 inactive protein_state "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
394 398 BRC4 chemical "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
400 404 FHTA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
406 412 H1525Q mutant "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
413 417 FQTA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
434 443 RAD51‐DNA complex_assembly "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
477 481 BRC7 chemical "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
483 487 FSTA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
489 495 S1979R mutant "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
496 500 FRTA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
501 506 BRCA2 protein "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
533 537 BRC3 chemical "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
539 543 FQTA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
545 551 T1430A mutant "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
552 556 FQAA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
557 566 RAD51:DNA complex_assembly "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
567 582 bandshift assay experimental_method "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
593 601 inactive protein_state "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
604 608 BRC3 chemical "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
610 614 FQTA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
616 622 T1430A mutant "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
623 627 FQAA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
628 648 Electron microscopic experimental_method "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
700 708 inactive protein_state "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
711 715 BRC1 chemical "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
717 721 FRTA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
723 729 T1011R mutant "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
730 734 FRRA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
735 740 BRCA2 protein "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
767 771 BRC2 chemical "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
773 777 FYSA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
779 785 S1221P mutant "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
786 790 FYPA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
791 796 BRCA2 protein "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
823 827 BRC2 chemical "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
829 833 FYSA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
835 841 S1221Y mutant "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
842 846 FYYA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
847 852 BRCA2 protein "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
879 884 RAD51 protein "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
886 890 FTTA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
892 896 A89E mutant "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
897 901 FTTE structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
902 921 Immunoprecipitation experimental_method "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
938 942 BRC4 chemical "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
944 948 FHTA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
950 956 A1527S mutant "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
957 961 FHTS structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
978 987 RAD51‐DNA complex_assembly "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
1007 1015 inactive protein_state "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE
4 13 wild‐type protein_state The wild‐type FxxA sequence is indicated in parenthesis. TABLE
14 18 FxxA structure_element The wild‐type FxxA sequence is indicated in parenthesis. TABLE
51 71 systematic mutations experimental_method In this work, we report the most detailed study of systematic mutations of peptides to probe the FxxA‐binding motif to date. ABBR
97 115 FxxA‐binding motif structure_element In this work, we report the most detailed study of systematic mutations of peptides to probe the FxxA‐binding motif to date. ABBR
27 40 tetrapeptides chemical We have chosen to focus on tetrapeptides, which allows us to examine the effect of mutation on the fundamental unit of binding, FxxA, rather than in the context of either the BRC repeat or self‐oligomerisation sequence. ABBR
83 91 mutation experimental_method We have chosen to focus on tetrapeptides, which allows us to examine the effect of mutation on the fundamental unit of binding, FxxA, rather than in the context of either the BRC repeat or self‐oligomerisation sequence. ABBR
128 132 FxxA structure_element We have chosen to focus on tetrapeptides, which allows us to examine the effect of mutation on the fundamental unit of binding, FxxA, rather than in the context of either the BRC repeat or self‐oligomerisation sequence. ABBR
175 185 BRC repeat structure_element We have chosen to focus on tetrapeptides, which allows us to examine the effect of mutation on the fundamental unit of binding, FxxA, rather than in the context of either the BRC repeat or self‐oligomerisation sequence. ABBR
189 218 self‐oligomerisation sequence structure_element We have chosen to focus on tetrapeptides, which allows us to examine the effect of mutation on the fundamental unit of binding, FxxA, rather than in the context of either the BRC repeat or self‐oligomerisation sequence. ABBR
0 10 Affinities evidence Affinities of peptides were measured directly using Isothermal Titration Calorimetry (ITC) and the structures of many of the peptides bound to humanised RadA were determined by X‐ray crystallography. ABBR
52 84 Isothermal Titration Calorimetry experimental_method Affinities of peptides were measured directly using Isothermal Titration Calorimetry (ITC) and the structures of many of the peptides bound to humanised RadA were determined by X‐ray crystallography. ABBR
86 89 ITC experimental_method Affinities of peptides were measured directly using Isothermal Titration Calorimetry (ITC) and the structures of many of the peptides bound to humanised RadA were determined by X‐ray crystallography. ABBR
99 109 structures evidence Affinities of peptides were measured directly using Isothermal Titration Calorimetry (ITC) and the structures of many of the peptides bound to humanised RadA were determined by X‐ray crystallography. ABBR
134 142 bound to protein_state Affinities of peptides were measured directly using Isothermal Titration Calorimetry (ITC) and the structures of many of the peptides bound to humanised RadA were determined by X‐ray crystallography. ABBR
143 152 humanised protein_state Affinities of peptides were measured directly using Isothermal Titration Calorimetry (ITC) and the structures of many of the peptides bound to humanised RadA were determined by X‐ray crystallography. ABBR
153 157 RadA protein Affinities of peptides were measured directly using Isothermal Titration Calorimetry (ITC) and the structures of many of the peptides bound to humanised RadA were determined by X‐ray crystallography. ABBR
177 198 X‐ray crystallography experimental_method Affinities of peptides were measured directly using Isothermal Titration Calorimetry (ITC) and the structures of many of the peptides bound to humanised RadA were determined by X‐ray crystallography. ABBR
11 14 ITC experimental_method The use of ITC is generally perceived as a gold‐standard in protein–ligand characterisation, rather than a competitive assay which may be prone to aggregation artefacts. ABBR
107 124 competitive assay experimental_method The use of ITC is generally perceived as a gold‐standard in protein–ligand characterisation, rather than a competitive assay which may be prone to aggregation artefacts. ABBR
0 9 Wild‐type protein_state Wild‐type human RAD51, however, is a heterogeneous mixture of oligomers and when monomerised by mutation, is highly unstable. ABBR
10 15 human species Wild‐type human RAD51, however, is a heterogeneous mixture of oligomers and when monomerised by mutation, is highly unstable. ABBR
16 21 RAD51 protein Wild‐type human RAD51, however, is a heterogeneous mixture of oligomers and when monomerised by mutation, is highly unstable. ABBR
62 71 oligomers oligomeric_state Wild‐type human RAD51, however, is a heterogeneous mixture of oligomers and when monomerised by mutation, is highly unstable. ABBR
81 92 monomerised oligomeric_state Wild‐type human RAD51, however, is a heterogeneous mixture of oligomers and when monomerised by mutation, is highly unstable. ABBR
96 104 mutation experimental_method Wild‐type human RAD51, however, is a heterogeneous mixture of oligomers and when monomerised by mutation, is highly unstable. ABBR
109 124 highly unstable protein_state Wild‐type human RAD51, however, is a heterogeneous mixture of oligomers and when monomerised by mutation, is highly unstable. ABBR
56 62 stable protein_state In this context, we have previously reported the use of stable monomeric forms of RAD51, humanised from Pyrococcus furiosus homologue RadA, for ITC experiments and X‐ray crystallography 8, 15. ABBR
63 72 monomeric oligomeric_state In this context, we have previously reported the use of stable monomeric forms of RAD51, humanised from Pyrococcus furiosus homologue RadA, for ITC experiments and X‐ray crystallography 8, 15. ABBR
82 87 RAD51 protein In this context, we have previously reported the use of stable monomeric forms of RAD51, humanised from Pyrococcus furiosus homologue RadA, for ITC experiments and X‐ray crystallography 8, 15. ABBR
89 98 humanised protein_state In this context, we have previously reported the use of stable monomeric forms of RAD51, humanised from Pyrococcus furiosus homologue RadA, for ITC experiments and X‐ray crystallography 8, 15. ABBR
104 123 Pyrococcus furiosus species In this context, we have previously reported the use of stable monomeric forms of RAD51, humanised from Pyrococcus furiosus homologue RadA, for ITC experiments and X‐ray crystallography 8, 15. ABBR
134 138 RadA protein In this context, we have previously reported the use of stable monomeric forms of RAD51, humanised from Pyrococcus furiosus homologue RadA, for ITC experiments and X‐ray crystallography 8, 15. ABBR
144 147 ITC experimental_method In this context, we have previously reported the use of stable monomeric forms of RAD51, humanised from Pyrococcus furiosus homologue RadA, for ITC experiments and X‐ray crystallography 8, 15. ABBR
164 185 X‐ray crystallography experimental_method In this context, we have previously reported the use of stable monomeric forms of RAD51, humanised from Pyrococcus furiosus homologue RadA, for ITC experiments and X‐ray crystallography 8, 15. ABBR
16 20 FxxA structure_element Conservation of FxxA motif (A) BRC4 peptide (green cartoon) bound to truncated human RAD51 (grey surface) (PDB: 1n0w, 11). FIG
31 35 BRC4 chemical Conservation of FxxA motif (A) BRC4 peptide (green cartoon) bound to truncated human RAD51 (grey surface) (PDB: 1n0w, 11). FIG
60 68 bound to protein_state Conservation of FxxA motif (A) BRC4 peptide (green cartoon) bound to truncated human RAD51 (grey surface) (PDB: 1n0w, 11). FIG
69 78 truncated protein_state Conservation of FxxA motif (A) BRC4 peptide (green cartoon) bound to truncated human RAD51 (grey surface) (PDB: 1n0w, 11). FIG
79 84 human species Conservation of FxxA motif (A) BRC4 peptide (green cartoon) bound to truncated human RAD51 (grey surface) (PDB: 1n0w, 11). FIG
85 90 RAD51 protein Conservation of FxxA motif (A) BRC4 peptide (green cartoon) bound to truncated human RAD51 (grey surface) (PDB: 1n0w, 11). FIG
35 58 FxxA interaction pocket site The blue dashed box highlights the FxxA interaction pocket. FIG
41 46 RAD51 protein (B) Two interacting protein molecules of RAD51 from Saccharomyces cerevisiae are shown. FIG
52 76 Saccharomyces cerevisiae species (B) Two interacting protein molecules of RAD51 from Saccharomyces cerevisiae are shown. FIG
4 9 RAD51 protein One RAD51 (green cartoon) interacts with another molecule of RAD51 (grey and pink surface) via the FxxA pocket indicated by the dashed blue box. FIG
61 66 RAD51 protein One RAD51 (green cartoon) interacts with another molecule of RAD51 (grey and pink surface) via the FxxA pocket indicated by the dashed blue box. FIG
99 110 FxxA pocket site One RAD51 (green cartoon) interacts with another molecule of RAD51 (grey and pink surface) via the FxxA pocket indicated by the dashed blue box. FIG
29 34 RAD51 protein The N‐terminal domain of one RAD51 protomer is highlighted in pink for clarity and the green arrow indicates the location of this protomer's FxxA oligomerisation sequence (PDB: 1szp, 29). (C) Conservation of FxxA motif across the human BRC repeats and (D) across 21 eukaryotic RAD51s and 24 RadAs, with the size of the letters proportional to the degree of conservation. FIG
35 43 protomer oligomeric_state The N‐terminal domain of one RAD51 protomer is highlighted in pink for clarity and the green arrow indicates the location of this protomer's FxxA oligomerisation sequence (PDB: 1szp, 29). (C) Conservation of FxxA motif across the human BRC repeats and (D) across 21 eukaryotic RAD51s and 24 RadAs, with the size of the letters proportional to the degree of conservation. FIG
130 138 protomer oligomeric_state The N‐terminal domain of one RAD51 protomer is highlighted in pink for clarity and the green arrow indicates the location of this protomer's FxxA oligomerisation sequence (PDB: 1szp, 29). (C) Conservation of FxxA motif across the human BRC repeats and (D) across 21 eukaryotic RAD51s and 24 RadAs, with the size of the letters proportional to the degree of conservation. FIG
141 170 FxxA oligomerisation sequence structure_element The N‐terminal domain of one RAD51 protomer is highlighted in pink for clarity and the green arrow indicates the location of this protomer's FxxA oligomerisation sequence (PDB: 1szp, 29). (C) Conservation of FxxA motif across the human BRC repeats and (D) across 21 eukaryotic RAD51s and 24 RadAs, with the size of the letters proportional to the degree of conservation. FIG
208 212 FxxA structure_element The N‐terminal domain of one RAD51 protomer is highlighted in pink for clarity and the green arrow indicates the location of this protomer's FxxA oligomerisation sequence (PDB: 1szp, 29). (C) Conservation of FxxA motif across the human BRC repeats and (D) across 21 eukaryotic RAD51s and 24 RadAs, with the size of the letters proportional to the degree of conservation. FIG
230 235 human species The N‐terminal domain of one RAD51 protomer is highlighted in pink for clarity and the green arrow indicates the location of this protomer's FxxA oligomerisation sequence (PDB: 1szp, 29). (C) Conservation of FxxA motif across the human BRC repeats and (D) across 21 eukaryotic RAD51s and 24 RadAs, with the size of the letters proportional to the degree of conservation. FIG
236 247 BRC repeats structure_element The N‐terminal domain of one RAD51 protomer is highlighted in pink for clarity and the green arrow indicates the location of this protomer's FxxA oligomerisation sequence (PDB: 1szp, 29). (C) Conservation of FxxA motif across the human BRC repeats and (D) across 21 eukaryotic RAD51s and 24 RadAs, with the size of the letters proportional to the degree of conservation. FIG
266 276 eukaryotic taxonomy_domain The N‐terminal domain of one RAD51 protomer is highlighted in pink for clarity and the green arrow indicates the location of this protomer's FxxA oligomerisation sequence (PDB: 1szp, 29). (C) Conservation of FxxA motif across the human BRC repeats and (D) across 21 eukaryotic RAD51s and 24 RadAs, with the size of the letters proportional to the degree of conservation. FIG
277 283 RAD51s protein_type The N‐terminal domain of one RAD51 protomer is highlighted in pink for clarity and the green arrow indicates the location of this protomer's FxxA oligomerisation sequence (PDB: 1szp, 29). (C) Conservation of FxxA motif across the human BRC repeats and (D) across 21 eukaryotic RAD51s and 24 RadAs, with the size of the letters proportional to the degree of conservation. FIG
291 296 RadAs protein_type The N‐terminal domain of one RAD51 protomer is highlighted in pink for clarity and the green arrow indicates the location of this protomer's FxxA oligomerisation sequence (PDB: 1szp, 29). (C) Conservation of FxxA motif across the human BRC repeats and (D) across 21 eukaryotic RAD51s and 24 RadAs, with the size of the letters proportional to the degree of conservation. FIG
8 29 mutated and truncated experimental_method We have mutated and truncated the tetrapeptide epitope FHTA, and examined the effects both structurally and on the binding affinity with humanised RadA. As a comparative reference, we are using the FHTA sequence derived from the most tightly binding BRC repeat, BRC4 22. RESULTS
34 46 tetrapeptide chemical We have mutated and truncated the tetrapeptide epitope FHTA, and examined the effects both structurally and on the binding affinity with humanised RadA. As a comparative reference, we are using the FHTA sequence derived from the most tightly binding BRC repeat, BRC4 22. RESULTS
55 59 FHTA structure_element We have mutated and truncated the tetrapeptide epitope FHTA, and examined the effects both structurally and on the binding affinity with humanised RadA. As a comparative reference, we are using the FHTA sequence derived from the most tightly binding BRC repeat, BRC4 22. RESULTS
115 131 binding affinity evidence We have mutated and truncated the tetrapeptide epitope FHTA, and examined the effects both structurally and on the binding affinity with humanised RadA. As a comparative reference, we are using the FHTA sequence derived from the most tightly binding BRC repeat, BRC4 22. RESULTS
137 146 humanised protein_state We have mutated and truncated the tetrapeptide epitope FHTA, and examined the effects both structurally and on the binding affinity with humanised RadA. As a comparative reference, we are using the FHTA sequence derived from the most tightly binding BRC repeat, BRC4 22. RESULTS
147 151 RadA protein We have mutated and truncated the tetrapeptide epitope FHTA, and examined the effects both structurally and on the binding affinity with humanised RadA. As a comparative reference, we are using the FHTA sequence derived from the most tightly binding BRC repeat, BRC4 22. RESULTS
198 202 FHTA structure_element We have mutated and truncated the tetrapeptide epitope FHTA, and examined the effects both structurally and on the binding affinity with humanised RadA. As a comparative reference, we are using the FHTA sequence derived from the most tightly binding BRC repeat, BRC4 22. RESULTS
250 260 BRC repeat structure_element We have mutated and truncated the tetrapeptide epitope FHTA, and examined the effects both structurally and on the binding affinity with humanised RadA. As a comparative reference, we are using the FHTA sequence derived from the most tightly binding BRC repeat, BRC4 22. RESULTS
262 266 BRC4 chemical We have mutated and truncated the tetrapeptide epitope FHTA, and examined the effects both structurally and on the binding affinity with humanised RadA. As a comparative reference, we are using the FHTA sequence derived from the most tightly binding BRC repeat, BRC4 22. RESULTS
22 34 N‐acetylated protein_state The peptides used are N‐acetylated and C‐amide terminated in order to provide the most relevant peptide in the context of a longer peptide chain. RESULTS
49 52 K D evidence A summary of the peptide sequence, PDB codes and K D data measured by ITC with the corresponding ΔH and TΔS values are collated in Table 2. RESULTS
70 73 ITC experimental_method A summary of the peptide sequence, PDB codes and K D data measured by ITC with the corresponding ΔH and TΔS values are collated in Table 2. RESULTS
97 99 ΔH evidence A summary of the peptide sequence, PDB codes and K D data measured by ITC with the corresponding ΔH and TΔS values are collated in Table 2. RESULTS
104 107 TΔS evidence A summary of the peptide sequence, PDB codes and K D data measured by ITC with the corresponding ΔH and TΔS values are collated in Table 2. RESULTS
0 7 Phe1524 residue_name_number Phe1524 of BRC4 binds in a small surface pocket of human RAD51, defined by the hydrophobic side chains of residues Met158, Ile160, Ala192, Leu203 and Met210. RESULTS
11 15 BRC4 chemical Phe1524 of BRC4 binds in a small surface pocket of human RAD51, defined by the hydrophobic side chains of residues Met158, Ile160, Ala192, Leu203 and Met210. RESULTS
33 47 surface pocket site Phe1524 of BRC4 binds in a small surface pocket of human RAD51, defined by the hydrophobic side chains of residues Met158, Ile160, Ala192, Leu203 and Met210. RESULTS
51 56 human species Phe1524 of BRC4 binds in a small surface pocket of human RAD51, defined by the hydrophobic side chains of residues Met158, Ile160, Ala192, Leu203 and Met210. RESULTS
57 62 RAD51 protein Phe1524 of BRC4 binds in a small surface pocket of human RAD51, defined by the hydrophobic side chains of residues Met158, Ile160, Ala192, Leu203 and Met210. RESULTS
115 121 Met158 residue_name_number Phe1524 of BRC4 binds in a small surface pocket of human RAD51, defined by the hydrophobic side chains of residues Met158, Ile160, Ala192, Leu203 and Met210. RESULTS
123 129 Ile160 residue_name_number Phe1524 of BRC4 binds in a small surface pocket of human RAD51, defined by the hydrophobic side chains of residues Met158, Ile160, Ala192, Leu203 and Met210. RESULTS
131 137 Ala192 residue_name_number Phe1524 of BRC4 binds in a small surface pocket of human RAD51, defined by the hydrophobic side chains of residues Met158, Ile160, Ala192, Leu203 and Met210. RESULTS
139 145 Leu203 residue_name_number Phe1524 of BRC4 binds in a small surface pocket of human RAD51, defined by the hydrophobic side chains of residues Met158, Ile160, Ala192, Leu203 and Met210. RESULTS
150 156 Met210 residue_name_number Phe1524 of BRC4 binds in a small surface pocket of human RAD51, defined by the hydrophobic side chains of residues Met158, Ile160, Ala192, Leu203 and Met210. RESULTS
15 31 highly conserved protein_state The residue is highly conserved across BRC repeats and oligomerisation sequences. RESULTS
39 50 BRC repeats structure_element The residue is highly conserved across BRC repeats and oligomerisation sequences. RESULTS
55 80 oligomerisation sequences structure_element The residue is highly conserved across BRC repeats and oligomerisation sequences. RESULTS
26 35 truncated protein_state Consistent with this, the truncated HTA tripeptide could not be detected to bind to humanised, monomeric RadA, HumRadA2 (Table 2, entry 13). RESULTS
36 39 HTA structure_element Consistent with this, the truncated HTA tripeptide could not be detected to bind to humanised, monomeric RadA, HumRadA2 (Table 2, entry 13). RESULTS
40 50 tripeptide chemical Consistent with this, the truncated HTA tripeptide could not be detected to bind to humanised, monomeric RadA, HumRadA2 (Table 2, entry 13). RESULTS
84 93 humanised protein_state Consistent with this, the truncated HTA tripeptide could not be detected to bind to humanised, monomeric RadA, HumRadA2 (Table 2, entry 13). RESULTS
95 104 monomeric oligomeric_state Consistent with this, the truncated HTA tripeptide could not be detected to bind to humanised, monomeric RadA, HumRadA2 (Table 2, entry 13). RESULTS
105 109 RadA protein Consistent with this, the truncated HTA tripeptide could not be detected to bind to humanised, monomeric RadA, HumRadA2 (Table 2, entry 13). RESULTS
111 119 HumRadA2 mutant Consistent with this, the truncated HTA tripeptide could not be detected to bind to humanised, monomeric RadA, HumRadA2 (Table 2, entry 13). RESULTS
53 65 substituting experimental_method As previously discussed, there is some evidence that substituting a tryptophan for the phenylalanine at this position was tolerated in the context of BRC4 12. RESULTS
68 78 tryptophan residue_name As previously discussed, there is some evidence that substituting a tryptophan for the phenylalanine at this position was tolerated in the context of BRC4 12. RESULTS
87 100 phenylalanine residue_name As previously discussed, there is some evidence that substituting a tryptophan for the phenylalanine at this position was tolerated in the context of BRC4 12. RESULTS
150 154 BRC4 chemical As previously discussed, there is some evidence that substituting a tryptophan for the phenylalanine at this position was tolerated in the context of BRC4 12. RESULTS
15 19 WHTA structure_element Therefore, the WHTA peptide was tested and found to not only be tolerated, but to increase the binding affinity of the peptide approximately threefold. RESULTS
95 111 binding affinity evidence Therefore, the WHTA peptide was tested and found to not only be tolerated, but to increase the binding affinity of the peptide approximately threefold. RESULTS
27 39 tetrapeptide chemical The second position of the tetrapeptide was found to be largely invariant to changes in the side chains that were investigated. RESULTS
43 48 RAD51 protein The residue makes no interactions with the RAD51 protein, but may make an internal hydrogen bond with Thr1520 in the context of BRC4, Fig. 3A. RESULTS
83 96 hydrogen bond bond_interaction The residue makes no interactions with the RAD51 protein, but may make an internal hydrogen bond with Thr1520 in the context of BRC4, Fig. 3A. RESULTS
102 109 Thr1520 residue_name_number The residue makes no interactions with the RAD51 protein, but may make an internal hydrogen bond with Thr1520 in the context of BRC4, Fig. 3A. RESULTS
128 132 BRC4 chemical The residue makes no interactions with the RAD51 protein, but may make an internal hydrogen bond with Thr1520 in the context of BRC4, Fig. 3A. RESULTS
0 9 Replacing experimental_method Replacing the histidine with an asparagine, chosen to potentially mimic the hydrogen bond donor–acceptor nature of histidine, resulted in a moderate, twofold decrease in potency (Table 2, entry 4). RESULTS
14 23 histidine residue_name Replacing the histidine with an asparagine, chosen to potentially mimic the hydrogen bond donor–acceptor nature of histidine, resulted in a moderate, twofold decrease in potency (Table 2, entry 4). RESULTS
32 42 asparagine residue_name Replacing the histidine with an asparagine, chosen to potentially mimic the hydrogen bond donor–acceptor nature of histidine, resulted in a moderate, twofold decrease in potency (Table 2, entry 4). RESULTS
76 89 hydrogen bond bond_interaction Replacing the histidine with an asparagine, chosen to potentially mimic the hydrogen bond donor–acceptor nature of histidine, resulted in a moderate, twofold decrease in potency (Table 2, entry 4). RESULTS
115 124 histidine residue_name Replacing the histidine with an asparagine, chosen to potentially mimic the hydrogen bond donor–acceptor nature of histidine, resulted in a moderate, twofold decrease in potency (Table 2, entry 4). RESULTS
0 8 Mutating experimental_method Mutating to an alanine, recapitulated the potency of FHTA, implying that the interactions made by histidine do not contribute overall to binding affinity (Table 2, entry 3). RESULTS
15 22 alanine residue_name Mutating to an alanine, recapitulated the potency of FHTA, implying that the interactions made by histidine do not contribute overall to binding affinity (Table 2, entry 3). RESULTS
53 57 FHTA structure_element Mutating to an alanine, recapitulated the potency of FHTA, implying that the interactions made by histidine do not contribute overall to binding affinity (Table 2, entry 3). RESULTS
98 107 histidine residue_name Mutating to an alanine, recapitulated the potency of FHTA, implying that the interactions made by histidine do not contribute overall to binding affinity (Table 2, entry 3). RESULTS
137 153 binding affinity evidence Mutating to an alanine, recapitulated the potency of FHTA, implying that the interactions made by histidine do not contribute overall to binding affinity (Table 2, entry 3). RESULTS
0 4 FPTA structure_element FPTA was also tested, but was found to have no affinity for the protein (Table 2, entry 5). RESULTS
47 55 affinity evidence FPTA was also tested, but was found to have no affinity for the protein (Table 2, entry 5). RESULTS
26 33 proline residue_name Modelling suggests that a proline in the second position would be expected to clash sterically with the surface of the protein, and provides a rationale for the lack of binding observed. RESULTS
0 9 Threonine residue_name Threonine was mutated to an alanine, resulting in only a moderately weaker K D (twofold, Table 2, entry 7). RESULTS
14 21 mutated experimental_method Threonine was mutated to an alanine, resulting in only a moderately weaker K D (twofold, Table 2, entry 7). RESULTS
28 35 alanine residue_name Threonine was mutated to an alanine, resulting in only a moderately weaker K D (twofold, Table 2, entry 7). RESULTS
75 78 K D evidence Threonine was mutated to an alanine, resulting in only a moderately weaker K D (twofold, Table 2, entry 7). RESULTS
20 32 tetrapeptide chemical In the context of a tetrapeptide at least, this result implies a lack of importance of a threonine at this position. RESULTS
89 98 threonine residue_name In the context of a tetrapeptide at least, this result implies a lack of importance of a threonine at this position. RESULTS
35 42 proline residue_name Interestingly, it was found that a proline at this position improved the affinity almost threefold, to 113 μm (Table 2, entry 6). RESULTS
73 81 affinity evidence Interestingly, it was found that a proline at this position improved the affinity almost threefold, to 113 μm (Table 2, entry 6). RESULTS
16 24 mutation experimental_method This beneficial mutation was incorporated with another previously identified variant to produce the peptide WHPA. RESULTS
108 112 WHPA structure_element This beneficial mutation was incorporated with another previously identified variant to produce the peptide WHPA. RESULTS
28 41 phenylalanine residue_name While the importance of the phenylalanine may be possible to predict from examination of the crystal structure, the alanine appears to be of much less importance in this regard. RESULTS
93 110 crystal structure evidence While the importance of the phenylalanine may be possible to predict from examination of the crystal structure, the alanine appears to be of much less importance in this regard. RESULTS
116 123 alanine residue_name While the importance of the phenylalanine may be possible to predict from examination of the crystal structure, the alanine appears to be of much less importance in this regard. RESULTS
18 34 highly conserved protein_state It is, however, a highly conserved residue and clearly of interest for systematic mutation. RESULTS
0 8 Removing experimental_method Removing the alanine residue entirely produced the truncated tripeptide FHT, which did not bind (Table 2, entry 12). RESULTS
13 20 alanine residue_name Removing the alanine residue entirely produced the truncated tripeptide FHT, which did not bind (Table 2, entry 12). RESULTS
51 60 truncated protein_state Removing the alanine residue entirely produced the truncated tripeptide FHT, which did not bind (Table 2, entry 12). RESULTS
61 71 tripeptide chemical Removing the alanine residue entirely produced the truncated tripeptide FHT, which did not bind (Table 2, entry 12). RESULTS
72 75 FHT structure_element Removing the alanine residue entirely produced the truncated tripeptide FHT, which did not bind (Table 2, entry 12). RESULTS
26 46 α‐amino butyric acid chemical The unnatural amino acid, α‐amino butyric acid (U), was introduced at the fourth position, positioning an ethyl group into the alanine pocket (Table 2, entry 9). RESULTS
48 49 U chemical The unnatural amino acid, α‐amino butyric acid (U), was introduced at the fourth position, positioning an ethyl group into the alanine pocket (Table 2, entry 9). RESULTS
127 141 alanine pocket site The unnatural amino acid, α‐amino butyric acid (U), was introduced at the fourth position, positioning an ethyl group into the alanine pocket (Table 2, entry 9). RESULTS
50 58 affinity evidence Perhaps surprisingly, it was accommodated and the affinity dropped only by twofold as compared to FHTA. RESULTS
98 102 FHTA structure_element Perhaps surprisingly, it was accommodated and the affinity dropped only by twofold as compared to FHTA. RESULTS
21 29 removing experimental_method The effect of simply removing the β‐carbon of alanine, by mutation to glycine (FHTG), produced an approximately sixfold drop in binding affinity (Table 2, entry 8). RESULTS
46 53 alanine residue_name The effect of simply removing the β‐carbon of alanine, by mutation to glycine (FHTG), produced an approximately sixfold drop in binding affinity (Table 2, entry 8). RESULTS
58 69 mutation to experimental_method The effect of simply removing the β‐carbon of alanine, by mutation to glycine (FHTG), produced an approximately sixfold drop in binding affinity (Table 2, entry 8). RESULTS
70 77 glycine residue_name The effect of simply removing the β‐carbon of alanine, by mutation to glycine (FHTG), produced an approximately sixfold drop in binding affinity (Table 2, entry 8). RESULTS
79 83 FHTG structure_element The effect of simply removing the β‐carbon of alanine, by mutation to glycine (FHTG), produced an approximately sixfold drop in binding affinity (Table 2, entry 8). RESULTS
128 144 binding affinity evidence The effect of simply removing the β‐carbon of alanine, by mutation to glycine (FHTG), produced an approximately sixfold drop in binding affinity (Table 2, entry 8). RESULTS
42 49 alanine residue_name This is in line with the observation that alanine is not 100% conserved and some archeal RadA proteins contain a glycine in the place of alanine 23. RESULTS
53 71 not 100% conserved protein_state This is in line with the observation that alanine is not 100% conserved and some archeal RadA proteins contain a glycine in the place of alanine 23. RESULTS
81 88 archeal taxonomy_domain This is in line with the observation that alanine is not 100% conserved and some archeal RadA proteins contain a glycine in the place of alanine 23. RESULTS
89 102 RadA proteins protein_type This is in line with the observation that alanine is not 100% conserved and some archeal RadA proteins contain a glycine in the place of alanine 23. RESULTS
113 120 glycine residue_name This is in line with the observation that alanine is not 100% conserved and some archeal RadA proteins contain a glycine in the place of alanine 23. RESULTS
137 144 alanine residue_name This is in line with the observation that alanine is not 100% conserved and some archeal RadA proteins contain a glycine in the place of alanine 23. RESULTS
0 27 Structural characterisation experimental_method Structural characterisation of peptide complexes RESULTS
0 10 Structures evidence Structures of the key tetrapeptides were solved by soaking into crystals of a humanised form of RAD51, HumRadA1, which we have previously reported as a convenient surrogate system for RAD51 crystallography 15. RESULTS
22 35 tetrapeptides chemical Structures of the key tetrapeptides were solved by soaking into crystals of a humanised form of RAD51, HumRadA1, which we have previously reported as a convenient surrogate system for RAD51 crystallography 15. RESULTS
51 63 soaking into experimental_method Structures of the key tetrapeptides were solved by soaking into crystals of a humanised form of RAD51, HumRadA1, which we have previously reported as a convenient surrogate system for RAD51 crystallography 15. RESULTS
64 72 crystals evidence Structures of the key tetrapeptides were solved by soaking into crystals of a humanised form of RAD51, HumRadA1, which we have previously reported as a convenient surrogate system for RAD51 crystallography 15. RESULTS
78 87 humanised protein_state Structures of the key tetrapeptides were solved by soaking into crystals of a humanised form of RAD51, HumRadA1, which we have previously reported as a convenient surrogate system for RAD51 crystallography 15. RESULTS
96 101 RAD51 protein Structures of the key tetrapeptides were solved by soaking into crystals of a humanised form of RAD51, HumRadA1, which we have previously reported as a convenient surrogate system for RAD51 crystallography 15. RESULTS
103 111 HumRadA1 mutant Structures of the key tetrapeptides were solved by soaking into crystals of a humanised form of RAD51, HumRadA1, which we have previously reported as a convenient surrogate system for RAD51 crystallography 15. RESULTS
184 189 RAD51 protein Structures of the key tetrapeptides were solved by soaking into crystals of a humanised form of RAD51, HumRadA1, which we have previously reported as a convenient surrogate system for RAD51 crystallography 15. RESULTS
190 205 crystallography experimental_method Structures of the key tetrapeptides were solved by soaking into crystals of a humanised form of RAD51, HumRadA1, which we have previously reported as a convenient surrogate system for RAD51 crystallography 15. RESULTS
57 78 crystallographic data evidence The corresponding PDB codes are indicated in Table 2 and crystallographic data are found in the Supporting Information. RESULTS
4 14 structures evidence All structures are of high resolution (1.2–1.7 Å) and the electron density for the peptide was clearly visible after the first refinement using unliganded RadA coordinates (Fig. S1). RESULTS
58 74 electron density evidence All structures are of high resolution (1.2–1.7 Å) and the electron density for the peptide was clearly visible after the first refinement using unliganded RadA coordinates (Fig. S1). RESULTS
144 154 unliganded protein_state All structures are of high resolution (1.2–1.7 Å) and the electron density for the peptide was clearly visible after the first refinement using unliganded RadA coordinates (Fig. S1). RESULTS
155 159 RadA protein All structures are of high resolution (1.2–1.7 Å) and the electron density for the peptide was clearly visible after the first refinement using unliganded RadA coordinates (Fig. S1). RESULTS
32 48 binding analysis experimental_method Some of the SAR observed in the binding analysis can be interpreted in terms of these X‐ray crystal structures. RESULTS
86 91 X‐ray experimental_method Some of the SAR observed in the binding analysis can be interpreted in terms of these X‐ray crystal structures. RESULTS
92 110 crystal structures evidence Some of the SAR observed in the binding analysis can be interpreted in terms of these X‐ray crystal structures. RESULTS
16 23 overlay experimental_method For example, an overlay of the bound poses of the ligands FHTA and FHPA (Fig. 2B) reveals a high similarity in the binding modes, indicating that the conformational rigidity conferred by the proline is compatible with the FHTA‐binding mode, and a reduction in an entropic penalty of binding may be the source of the improvement in affinity. RESULTS
58 62 FHTA structure_element For example, an overlay of the bound poses of the ligands FHTA and FHPA (Fig. 2B) reveals a high similarity in the binding modes, indicating that the conformational rigidity conferred by the proline is compatible with the FHTA‐binding mode, and a reduction in an entropic penalty of binding may be the source of the improvement in affinity. RESULTS
67 71 FHPA structure_element For example, an overlay of the bound poses of the ligands FHTA and FHPA (Fig. 2B) reveals a high similarity in the binding modes, indicating that the conformational rigidity conferred by the proline is compatible with the FHTA‐binding mode, and a reduction in an entropic penalty of binding may be the source of the improvement in affinity. RESULTS
191 198 proline residue_name For example, an overlay of the bound poses of the ligands FHTA and FHPA (Fig. 2B) reveals a high similarity in the binding modes, indicating that the conformational rigidity conferred by the proline is compatible with the FHTA‐binding mode, and a reduction in an entropic penalty of binding may be the source of the improvement in affinity. RESULTS
222 226 FHTA structure_element For example, an overlay of the bound poses of the ligands FHTA and FHPA (Fig. 2B) reveals a high similarity in the binding modes, indicating that the conformational rigidity conferred by the proline is compatible with the FHTA‐binding mode, and a reduction in an entropic penalty of binding may be the source of the improvement in affinity. RESULTS
263 279 entropic penalty evidence For example, an overlay of the bound poses of the ligands FHTA and FHPA (Fig. 2B) reveals a high similarity in the binding modes, indicating that the conformational rigidity conferred by the proline is compatible with the FHTA‐binding mode, and a reduction in an entropic penalty of binding may be the source of the improvement in affinity. RESULTS
331 339 affinity evidence For example, an overlay of the bound poses of the ligands FHTA and FHPA (Fig. 2B) reveals a high similarity in the binding modes, indicating that the conformational rigidity conferred by the proline is compatible with the FHTA‐binding mode, and a reduction in an entropic penalty of binding may be the source of the improvement in affinity. RESULTS
0 4 WHTA structure_element WHTA peptide shows a relative dislocation when compared to FHTA (Fig 2A), with the entire ligand backbone of WHTA shifted to accommodate the change in the position of the main chain carbon of the first residue, as the larger indole side chain fills the Phe pocket. RESULTS
59 63 FHTA structure_element WHTA peptide shows a relative dislocation when compared to FHTA (Fig 2A), with the entire ligand backbone of WHTA shifted to accommodate the change in the position of the main chain carbon of the first residue, as the larger indole side chain fills the Phe pocket. RESULTS
109 113 WHTA structure_element WHTA peptide shows a relative dislocation when compared to FHTA (Fig 2A), with the entire ligand backbone of WHTA shifted to accommodate the change in the position of the main chain carbon of the first residue, as the larger indole side chain fills the Phe pocket. RESULTS
253 263 Phe pocket site WHTA peptide shows a relative dislocation when compared to FHTA (Fig 2A), with the entire ligand backbone of WHTA shifted to accommodate the change in the position of the main chain carbon of the first residue, as the larger indole side chain fills the Phe pocket. RESULTS
44 51 alanine residue_name This shift is translated all the way to the alanine side chain. RESULTS
25 33 mutation experimental_method It is possible that this mutation is beneficial in the tetrapeptide context and neutral in the full‐length BRC4 context because the smaller peptide is less constrained and allowed to explore more conformations. RESULTS
55 67 tetrapeptide chemical It is possible that this mutation is beneficial in the tetrapeptide context and neutral in the full‐length BRC4 context because the smaller peptide is less constrained and allowed to explore more conformations. RESULTS
95 106 full‐length protein_state It is possible that this mutation is beneficial in the tetrapeptide context and neutral in the full‐length BRC4 context because the smaller peptide is less constrained and allowed to explore more conformations. RESULTS
107 111 BRC4 chemical It is possible that this mutation is beneficial in the tetrapeptide context and neutral in the full‐length BRC4 context because the smaller peptide is less constrained and allowed to explore more conformations. RESULTS
31 41 tryptophan residue_name An attempt to combine both the tryptophan and proline mutations, however, led to no improvement for WHPA peptide compared to FHTA. RESULTS
46 53 proline residue_name An attempt to combine both the tryptophan and proline mutations, however, led to no improvement for WHPA peptide compared to FHTA. RESULTS
54 63 mutations experimental_method An attempt to combine both the tryptophan and proline mutations, however, led to no improvement for WHPA peptide compared to FHTA. RESULTS
100 104 WHPA structure_element An attempt to combine both the tryptophan and proline mutations, however, led to no improvement for WHPA peptide compared to FHTA. RESULTS
125 129 FHTA structure_element An attempt to combine both the tryptophan and proline mutations, however, led to no improvement for WHPA peptide compared to FHTA. RESULTS
72 76 WHTA structure_element One possible explanation is that the ‘shifted’ binding mode observed in WHTA was not compatible with the conformational restriction that the proline of WHPA introduced. RESULTS
141 148 proline residue_name One possible explanation is that the ‘shifted’ binding mode observed in WHTA was not compatible with the conformational restriction that the proline of WHPA introduced. RESULTS
152 156 WHPA structure_element One possible explanation is that the ‘shifted’ binding mode observed in WHTA was not compatible with the conformational restriction that the proline of WHPA introduced. RESULTS
46 53 Overlay experimental_method Comparison of different peptide complexes (A) Overlay with FHTA (grey) and WHTA (purple) showing a small relative displacement of the peptide backbone. (B) Superposition of FHTA (grey) and FHPA (yellow), showing conservation of backbone orientation (C) Overlay of FHTU (green), FHTA (grey) and FHTG (cyan). FIG
59 63 FHTA structure_element Comparison of different peptide complexes (A) Overlay with FHTA (grey) and WHTA (purple) showing a small relative displacement of the peptide backbone. (B) Superposition of FHTA (grey) and FHPA (yellow), showing conservation of backbone orientation (C) Overlay of FHTU (green), FHTA (grey) and FHTG (cyan). FIG
75 79 WHTA structure_element Comparison of different peptide complexes (A) Overlay with FHTA (grey) and WHTA (purple) showing a small relative displacement of the peptide backbone. (B) Superposition of FHTA (grey) and FHPA (yellow), showing conservation of backbone orientation (C) Overlay of FHTU (green), FHTA (grey) and FHTG (cyan). FIG
156 169 Superposition experimental_method Comparison of different peptide complexes (A) Overlay with FHTA (grey) and WHTA (purple) showing a small relative displacement of the peptide backbone. (B) Superposition of FHTA (grey) and FHPA (yellow), showing conservation of backbone orientation (C) Overlay of FHTU (green), FHTA (grey) and FHTG (cyan). FIG
173 177 FHTA structure_element Comparison of different peptide complexes (A) Overlay with FHTA (grey) and WHTA (purple) showing a small relative displacement of the peptide backbone. (B) Superposition of FHTA (grey) and FHPA (yellow), showing conservation of backbone orientation (C) Overlay of FHTU (green), FHTA (grey) and FHTG (cyan). FIG
189 193 FHPA structure_element Comparison of different peptide complexes (A) Overlay with FHTA (grey) and WHTA (purple) showing a small relative displacement of the peptide backbone. (B) Superposition of FHTA (grey) and FHPA (yellow), showing conservation of backbone orientation (C) Overlay of FHTU (green), FHTA (grey) and FHTG (cyan). FIG
253 260 Overlay experimental_method Comparison of different peptide complexes (A) Overlay with FHTA (grey) and WHTA (purple) showing a small relative displacement of the peptide backbone. (B) Superposition of FHTA (grey) and FHPA (yellow), showing conservation of backbone orientation (C) Overlay of FHTU (green), FHTA (grey) and FHTG (cyan). FIG
264 268 FHTU structure_element Comparison of different peptide complexes (A) Overlay with FHTA (grey) and WHTA (purple) showing a small relative displacement of the peptide backbone. (B) Superposition of FHTA (grey) and FHPA (yellow), showing conservation of backbone orientation (C) Overlay of FHTU (green), FHTA (grey) and FHTG (cyan). FIG
278 282 FHTA structure_element Comparison of different peptide complexes (A) Overlay with FHTA (grey) and WHTA (purple) showing a small relative displacement of the peptide backbone. (B) Superposition of FHTA (grey) and FHPA (yellow), showing conservation of backbone orientation (C) Overlay of FHTU (green), FHTA (grey) and FHTG (cyan). FIG
294 298 FHTG structure_element Comparison of different peptide complexes (A) Overlay with FHTA (grey) and WHTA (purple) showing a small relative displacement of the peptide backbone. (B) Superposition of FHTA (grey) and FHPA (yellow), showing conservation of backbone orientation (C) Overlay of FHTU (green), FHTA (grey) and FHTG (cyan). FIG
4 22 thermodynamic data evidence The thermodynamic data of peptide binding are also shown in Table 2. Although we have both thermodynamic data and high‐quality X‐ray structural information for some of the mutant peptides, we do not attempt to interpret differences in thermodynamic profiles between ligands, that is, to analyse ΔΔH and ΔΔS. RESULTS
91 109 thermodynamic data evidence The thermodynamic data of peptide binding are also shown in Table 2. Although we have both thermodynamic data and high‐quality X‐ray structural information for some of the mutant peptides, we do not attempt to interpret differences in thermodynamic profiles between ligands, that is, to analyse ΔΔH and ΔΔS. RESULTS
127 132 X‐ray experimental_method The thermodynamic data of peptide binding are also shown in Table 2. Although we have both thermodynamic data and high‐quality X‐ray structural information for some of the mutant peptides, we do not attempt to interpret differences in thermodynamic profiles between ligands, that is, to analyse ΔΔH and ΔΔS. RESULTS
133 155 structural information evidence The thermodynamic data of peptide binding are also shown in Table 2. Although we have both thermodynamic data and high‐quality X‐ray structural information for some of the mutant peptides, we do not attempt to interpret differences in thermodynamic profiles between ligands, that is, to analyse ΔΔH and ΔΔS. RESULTS
172 178 mutant protein_state The thermodynamic data of peptide binding are also shown in Table 2. Although we have both thermodynamic data and high‐quality X‐ray structural information for some of the mutant peptides, we do not attempt to interpret differences in thermodynamic profiles between ligands, that is, to analyse ΔΔH and ΔΔS. RESULTS
179 187 peptides chemical The thermodynamic data of peptide binding are also shown in Table 2. Although we have both thermodynamic data and high‐quality X‐ray structural information for some of the mutant peptides, we do not attempt to interpret differences in thermodynamic profiles between ligands, that is, to analyse ΔΔH and ΔΔS. RESULTS
235 257 thermodynamic profiles evidence The thermodynamic data of peptide binding are also shown in Table 2. Although we have both thermodynamic data and high‐quality X‐ray structural information for some of the mutant peptides, we do not attempt to interpret differences in thermodynamic profiles between ligands, that is, to analyse ΔΔH and ΔΔS. RESULTS
295 298 ΔΔH evidence The thermodynamic data of peptide binding are also shown in Table 2. Although we have both thermodynamic data and high‐quality X‐ray structural information for some of the mutant peptides, we do not attempt to interpret differences in thermodynamic profiles between ligands, that is, to analyse ΔΔH and ΔΔS. RESULTS
303 306 ΔΔS evidence The thermodynamic data of peptide binding are also shown in Table 2. Although we have both thermodynamic data and high‐quality X‐ray structural information for some of the mutant peptides, we do not attempt to interpret differences in thermodynamic profiles between ligands, that is, to analyse ΔΔH and ΔΔS. RESULTS
9 11 ΔH evidence Although ΔH and ΔS are tabulated, the K Ds measured are relatively weak and necessarily performed under low c‐value conditions. RESULTS
16 18 ΔS evidence Although ΔH and ΔS are tabulated, the K Ds measured are relatively weak and necessarily performed under low c‐value conditions. RESULTS
38 42 K Ds evidence Although ΔH and ΔS are tabulated, the K Ds measured are relatively weak and necessarily performed under low c‐value conditions. RESULTS
87 89 ΔH evidence In this experimental regime, nonsigmoidal curves are generated and therefore errors in ΔH are expected to be much higher than the errors from model fitting given in Table 2 16. RESULTS
3 5 ΔS evidence As ΔS is derived from ΔG by subtracting ΔH, errors in ΔH will be correlated with errors in ΔS, giving rise to a ‘phantom’ enthalpy–entropy compensation. RESULTS
22 24 ΔG evidence As ΔS is derived from ΔG by subtracting ΔH, errors in ΔH will be correlated with errors in ΔS, giving rise to a ‘phantom’ enthalpy–entropy compensation. RESULTS
40 42 ΔH evidence As ΔS is derived from ΔG by subtracting ΔH, errors in ΔH will be correlated with errors in ΔS, giving rise to a ‘phantom’ enthalpy–entropy compensation. RESULTS
54 56 ΔH evidence As ΔS is derived from ΔG by subtracting ΔH, errors in ΔH will be correlated with errors in ΔS, giving rise to a ‘phantom’ enthalpy–entropy compensation. RESULTS
91 93 ΔS evidence As ΔS is derived from ΔG by subtracting ΔH, errors in ΔH will be correlated with errors in ΔS, giving rise to a ‘phantom’ enthalpy–entropy compensation. RESULTS
125 128 ΔΔH evidence Such effects have been discussed by Klebe 24 and Chodera and Mobley 25 and will frustrate attempts to interpret the measured ΔΔH and ΔΔS. RESULTS
133 136 ΔΔS evidence Such effects have been discussed by Klebe 24 and Chodera and Mobley 25 and will frustrate attempts to interpret the measured ΔΔH and ΔΔS. RESULTS
4 13 conserved protein_state The conserved phenylalanine and alanine residues of the FHTA sequence were both found to be essential for binding by ITC. RESULTS
14 27 phenylalanine residue_name The conserved phenylalanine and alanine residues of the FHTA sequence were both found to be essential for binding by ITC. RESULTS
32 39 alanine residue_name The conserved phenylalanine and alanine residues of the FHTA sequence were both found to be essential for binding by ITC. RESULTS
56 60 FHTA structure_element The conserved phenylalanine and alanine residues of the FHTA sequence were both found to be essential for binding by ITC. RESULTS
117 120 ITC experimental_method The conserved phenylalanine and alanine residues of the FHTA sequence were both found to be essential for binding by ITC. RESULTS
31 40 histidine residue_name Conversely the second position histidine residue, corresponding to the unconserved His1525 in the BRC4 sequence, could be mutated without significant effect on the peptide affinity. RESULTS
71 82 unconserved protein_state Conversely the second position histidine residue, corresponding to the unconserved His1525 in the BRC4 sequence, could be mutated without significant effect on the peptide affinity. RESULTS
83 90 His1525 residue_name_number Conversely the second position histidine residue, corresponding to the unconserved His1525 in the BRC4 sequence, could be mutated without significant effect on the peptide affinity. RESULTS
98 102 BRC4 chemical Conversely the second position histidine residue, corresponding to the unconserved His1525 in the BRC4 sequence, could be mutated without significant effect on the peptide affinity. RESULTS
122 129 mutated experimental_method Conversely the second position histidine residue, corresponding to the unconserved His1525 in the BRC4 sequence, could be mutated without significant effect on the peptide affinity. RESULTS
164 180 peptide affinity evidence Conversely the second position histidine residue, corresponding to the unconserved His1525 in the BRC4 sequence, could be mutated without significant effect on the peptide affinity. RESULTS
37 45 hot‐spot site The more general correlation between hot‐spot residues in protein–protein interactions and the high conservation of such residues has been previously reported 10, 26. RESULTS
95 112 high conservation protein_state The more general correlation between hot‐spot residues in protein–protein interactions and the high conservation of such residues has been previously reported 10, 26. RESULTS
28 44 highly conserved protein_state Interestingly, however, the highly conserved threonine residue could be mutated without affecting the peptide affinity. RESULTS
45 54 threonine residue_name Interestingly, however, the highly conserved threonine residue could be mutated without affecting the peptide affinity. RESULTS
72 79 mutated experimental_method Interestingly, however, the highly conserved threonine residue could be mutated without affecting the peptide affinity. RESULTS
102 118 peptide affinity evidence Interestingly, however, the highly conserved threonine residue could be mutated without affecting the peptide affinity. RESULTS
49 66 high conservation protein_state This unexpected result, in the light of its very high conservation in the BRC and oligomerisation sequences, begs the question of what the role of Thr1526 is and highlights a potential pitfall and need for caution in the experimental design of alanine mutation studies. RESULTS
74 77 BRC structure_element This unexpected result, in the light of its very high conservation in the BRC and oligomerisation sequences, begs the question of what the role of Thr1526 is and highlights a potential pitfall and need for caution in the experimental design of alanine mutation studies. RESULTS
82 107 oligomerisation sequences structure_element This unexpected result, in the light of its very high conservation in the BRC and oligomerisation sequences, begs the question of what the role of Thr1526 is and highlights a potential pitfall and need for caution in the experimental design of alanine mutation studies. RESULTS
147 154 Thr1526 residue_name_number This unexpected result, in the light of its very high conservation in the BRC and oligomerisation sequences, begs the question of what the role of Thr1526 is and highlights a potential pitfall and need for caution in the experimental design of alanine mutation studies. RESULTS
244 268 alanine mutation studies experimental_method This unexpected result, in the light of its very high conservation in the BRC and oligomerisation sequences, begs the question of what the role of Thr1526 is and highlights a potential pitfall and need for caution in the experimental design of alanine mutation studies. RESULTS
7 11 FHTA structure_element As the FHTA peptide is potentially a surrogate peptide for both the BRC repeat peptides and the RAD51 self‐oligomerisation peptide, it is useful to examine the role of Thr1526 (BRC4) and the analogous Thr87 (RAD51) in both binding contexts in more detail. RESULTS
12 19 peptide chemical As the FHTA peptide is potentially a surrogate peptide for both the BRC repeat peptides and the RAD51 self‐oligomerisation peptide, it is useful to examine the role of Thr1526 (BRC4) and the analogous Thr87 (RAD51) in both binding contexts in more detail. RESULTS
68 78 BRC repeat structure_element As the FHTA peptide is potentially a surrogate peptide for both the BRC repeat peptides and the RAD51 self‐oligomerisation peptide, it is useful to examine the role of Thr1526 (BRC4) and the analogous Thr87 (RAD51) in both binding contexts in more detail. RESULTS
96 101 RAD51 protein As the FHTA peptide is potentially a surrogate peptide for both the BRC repeat peptides and the RAD51 self‐oligomerisation peptide, it is useful to examine the role of Thr1526 (BRC4) and the analogous Thr87 (RAD51) in both binding contexts in more detail. RESULTS
102 130 self‐oligomerisation peptide structure_element As the FHTA peptide is potentially a surrogate peptide for both the BRC repeat peptides and the RAD51 self‐oligomerisation peptide, it is useful to examine the role of Thr1526 (BRC4) and the analogous Thr87 (RAD51) in both binding contexts in more detail. RESULTS
168 175 Thr1526 residue_name_number As the FHTA peptide is potentially a surrogate peptide for both the BRC repeat peptides and the RAD51 self‐oligomerisation peptide, it is useful to examine the role of Thr1526 (BRC4) and the analogous Thr87 (RAD51) in both binding contexts in more detail. RESULTS
177 181 BRC4 chemical As the FHTA peptide is potentially a surrogate peptide for both the BRC repeat peptides and the RAD51 self‐oligomerisation peptide, it is useful to examine the role of Thr1526 (BRC4) and the analogous Thr87 (RAD51) in both binding contexts in more detail. RESULTS
201 206 Thr87 residue_name_number As the FHTA peptide is potentially a surrogate peptide for both the BRC repeat peptides and the RAD51 self‐oligomerisation peptide, it is useful to examine the role of Thr1526 (BRC4) and the analogous Thr87 (RAD51) in both binding contexts in more detail. RESULTS
208 213 RAD51 protein As the FHTA peptide is potentially a surrogate peptide for both the BRC repeat peptides and the RAD51 self‐oligomerisation peptide, it is useful to examine the role of Thr1526 (BRC4) and the analogous Thr87 (RAD51) in both binding contexts in more detail. RESULTS
9 18 structure evidence Only one structure of BRC4 is published in complex with human RAD51 (PDB: 1n0w). RESULTS
22 26 BRC4 chemical Only one structure of BRC4 is published in complex with human RAD51 (PDB: 1n0w). RESULTS
40 55 in complex with protein_state Only one structure of BRC4 is published in complex with human RAD51 (PDB: 1n0w). RESULTS
56 61 human species Only one structure of BRC4 is published in complex with human RAD51 (PDB: 1n0w). RESULTS
62 67 RAD51 protein Only one structure of BRC4 is published in complex with human RAD51 (PDB: 1n0w). RESULTS
36 40 BRC4 chemical Figure 3A shows the binding pose of BRC4 when bound to RAD51 and the intrapeptide hydrogen bonds that are made by BRC4. RESULTS
46 54 bound to protein_state Figure 3A shows the binding pose of BRC4 when bound to RAD51 and the intrapeptide hydrogen bonds that are made by BRC4. RESULTS
55 60 RAD51 protein Figure 3A shows the binding pose of BRC4 when bound to RAD51 and the intrapeptide hydrogen bonds that are made by BRC4. RESULTS
82 96 hydrogen bonds bond_interaction Figure 3A shows the binding pose of BRC4 when bound to RAD51 and the intrapeptide hydrogen bonds that are made by BRC4. RESULTS
114 118 BRC4 chemical Figure 3A shows the binding pose of BRC4 when bound to RAD51 and the intrapeptide hydrogen bonds that are made by BRC4. RESULTS
6 13 Phe1524 residue_name_number While Phe1524 and Ala1527 are buried in hydrophobic pockets on the surface, His1525 is close enough to form a hydrogen bond with the carbonyl of Thr1520, but the rotamer of His1525, supported by clearly positioned water molecules, is not compatible with hydrogen bonding. RESULTS
18 25 Ala1527 residue_name_number While Phe1524 and Ala1527 are buried in hydrophobic pockets on the surface, His1525 is close enough to form a hydrogen bond with the carbonyl of Thr1520, but the rotamer of His1525, supported by clearly positioned water molecules, is not compatible with hydrogen bonding. RESULTS
40 59 hydrophobic pockets site While Phe1524 and Ala1527 are buried in hydrophobic pockets on the surface, His1525 is close enough to form a hydrogen bond with the carbonyl of Thr1520, but the rotamer of His1525, supported by clearly positioned water molecules, is not compatible with hydrogen bonding. RESULTS
76 83 His1525 residue_name_number While Phe1524 and Ala1527 are buried in hydrophobic pockets on the surface, His1525 is close enough to form a hydrogen bond with the carbonyl of Thr1520, but the rotamer of His1525, supported by clearly positioned water molecules, is not compatible with hydrogen bonding. RESULTS
110 123 hydrogen bond bond_interaction While Phe1524 and Ala1527 are buried in hydrophobic pockets on the surface, His1525 is close enough to form a hydrogen bond with the carbonyl of Thr1520, but the rotamer of His1525, supported by clearly positioned water molecules, is not compatible with hydrogen bonding. RESULTS
145 152 Thr1520 residue_name_number While Phe1524 and Ala1527 are buried in hydrophobic pockets on the surface, His1525 is close enough to form a hydrogen bond with the carbonyl of Thr1520, but the rotamer of His1525, supported by clearly positioned water molecules, is not compatible with hydrogen bonding. RESULTS
173 180 His1525 residue_name_number While Phe1524 and Ala1527 are buried in hydrophobic pockets on the surface, His1525 is close enough to form a hydrogen bond with the carbonyl of Thr1520, but the rotamer of His1525, supported by clearly positioned water molecules, is not compatible with hydrogen bonding. RESULTS
214 219 water chemical While Phe1524 and Ala1527 are buried in hydrophobic pockets on the surface, His1525 is close enough to form a hydrogen bond with the carbonyl of Thr1520, but the rotamer of His1525, supported by clearly positioned water molecules, is not compatible with hydrogen bonding. RESULTS
254 270 hydrogen bonding bond_interaction While Phe1524 and Ala1527 are buried in hydrophobic pockets on the surface, His1525 is close enough to form a hydrogen bond with the carbonyl of Thr1520, but the rotamer of His1525, supported by clearly positioned water molecules, is not compatible with hydrogen bonding. RESULTS
6 13 Thr1520 residue_name_number Also, Thr1520 is constrained by crystal contacts in this structure. RESULTS
57 66 structure evidence Also, Thr1520 is constrained by crystal contacts in this structure. RESULTS
0 20 Lack of conservation protein_state Lack of conservation of this residue supports the idea that this interaction is not crucial for RAD51:BRC repeat binding. RESULTS
96 112 RAD51:BRC repeat complex_assembly Lack of conservation of this residue supports the idea that this interaction is not crucial for RAD51:BRC repeat binding. RESULTS
23 27 BRC4 chemical (A) Highlight of intra‐BRC4 interactions when bound to RAD51 (omitted for clarity) (PDB: 1n0w), with key residues shown in colour. (B) Intrapeptide interactions from oligomerisation epitope of S. cerevisiae RAD51 when bound to next RAD51 in the filament (PDB: 1szp). FIG
46 54 bound to protein_state (A) Highlight of intra‐BRC4 interactions when bound to RAD51 (omitted for clarity) (PDB: 1n0w), with key residues shown in colour. (B) Intrapeptide interactions from oligomerisation epitope of S. cerevisiae RAD51 when bound to next RAD51 in the filament (PDB: 1szp). FIG
55 60 RAD51 protein (A) Highlight of intra‐BRC4 interactions when bound to RAD51 (omitted for clarity) (PDB: 1n0w), with key residues shown in colour. (B) Intrapeptide interactions from oligomerisation epitope of S. cerevisiae RAD51 when bound to next RAD51 in the filament (PDB: 1szp). FIG
166 189 oligomerisation epitope structure_element (A) Highlight of intra‐BRC4 interactions when bound to RAD51 (omitted for clarity) (PDB: 1n0w), with key residues shown in colour. (B) Intrapeptide interactions from oligomerisation epitope of S. cerevisiae RAD51 when bound to next RAD51 in the filament (PDB: 1szp). FIG
193 206 S. cerevisiae species (A) Highlight of intra‐BRC4 interactions when bound to RAD51 (omitted for clarity) (PDB: 1n0w), with key residues shown in colour. (B) Intrapeptide interactions from oligomerisation epitope of S. cerevisiae RAD51 when bound to next RAD51 in the filament (PDB: 1szp). FIG
208 213 RAD51 protein (A) Highlight of intra‐BRC4 interactions when bound to RAD51 (omitted for clarity) (PDB: 1n0w), with key residues shown in colour. (B) Intrapeptide interactions from oligomerisation epitope of S. cerevisiae RAD51 when bound to next RAD51 in the filament (PDB: 1szp). FIG
219 227 bound to protein_state (A) Highlight of intra‐BRC4 interactions when bound to RAD51 (omitted for clarity) (PDB: 1n0w), with key residues shown in colour. (B) Intrapeptide interactions from oligomerisation epitope of S. cerevisiae RAD51 when bound to next RAD51 in the filament (PDB: 1szp). FIG
233 238 RAD51 protein (A) Highlight of intra‐BRC4 interactions when bound to RAD51 (omitted for clarity) (PDB: 1n0w), with key residues shown in colour. (B) Intrapeptide interactions from oligomerisation epitope of S. cerevisiae RAD51 when bound to next RAD51 in the filament (PDB: 1szp). FIG
33 46 S. cerevisiae species Residue numbering relates to the S. cerevisiae RAD51 protein, the corresponding human residues are in parentheses. FIG
48 53 RAD51 protein Residue numbering relates to the S. cerevisiae RAD51 protein, the corresponding human residues are in parentheses. FIG
81 86 human species Residue numbering relates to the S. cerevisiae RAD51 protein, the corresponding human residues are in parentheses. FIG
9 18 threonine residue_name Either a threonine or serine is most commonly found in the third position of the FxxA motif. RESULTS
22 28 serine residue_name Either a threonine or serine is most commonly found in the third position of the FxxA motif. RESULTS
81 85 FxxA structure_element Either a threonine or serine is most commonly found in the third position of the FxxA motif. RESULTS
0 7 Thr1526 residue_name_number Thr1526 makes no direct interactions with the RAD51 protein, but instead forms a hydrogen bond network with the highly conserved S1528 and K1530 (Fig. 1C). RESULTS
46 51 RAD51 protein Thr1526 makes no direct interactions with the RAD51 protein, but instead forms a hydrogen bond network with the highly conserved S1528 and K1530 (Fig. 1C). RESULTS
81 102 hydrogen bond network bond_interaction Thr1526 makes no direct interactions with the RAD51 protein, but instead forms a hydrogen bond network with the highly conserved S1528 and K1530 (Fig. 1C). RESULTS
112 128 highly conserved protein_state Thr1526 makes no direct interactions with the RAD51 protein, but instead forms a hydrogen bond network with the highly conserved S1528 and K1530 (Fig. 1C). RESULTS
129 134 S1528 residue_name_number Thr1526 makes no direct interactions with the RAD51 protein, but instead forms a hydrogen bond network with the highly conserved S1528 and K1530 (Fig. 1C). RESULTS
139 144 K1530 residue_name_number Thr1526 makes no direct interactions with the RAD51 protein, but instead forms a hydrogen bond network with the highly conserved S1528 and K1530 (Fig. 1C). RESULTS
4 31 high degree of conservation protein_state The high degree of conservation of these three residues suggests an important possible role in facilitating a turn and stabilising the conformation of the peptide as it continues its way to a second interaction site on the side of RAD51. RESULTS
199 215 interaction site site The high degree of conservation of these three residues suggests an important possible role in facilitating a turn and stabilising the conformation of the peptide as it continues its way to a second interaction site on the side of RAD51. RESULTS
231 236 RAD51 protein The high degree of conservation of these three residues suggests an important possible role in facilitating a turn and stabilising the conformation of the peptide as it continues its way to a second interaction site on the side of RAD51. RESULTS
34 45 RAD51:RAD51 complex_assembly With respect to understanding the RAD51:RAD51 interaction, no human crystal structure has been published, however, several oligomeric structures of archaeal RadA as well that of Saccharomyces cerevisiae RAD51 have been reported 27, 28, 29. RESULTS
62 67 human species With respect to understanding the RAD51:RAD51 interaction, no human crystal structure has been published, however, several oligomeric structures of archaeal RadA as well that of Saccharomyces cerevisiae RAD51 have been reported 27, 28, 29. RESULTS
68 85 crystal structure evidence With respect to understanding the RAD51:RAD51 interaction, no human crystal structure has been published, however, several oligomeric structures of archaeal RadA as well that of Saccharomyces cerevisiae RAD51 have been reported 27, 28, 29. RESULTS
134 144 structures evidence With respect to understanding the RAD51:RAD51 interaction, no human crystal structure has been published, however, several oligomeric structures of archaeal RadA as well that of Saccharomyces cerevisiae RAD51 have been reported 27, 28, 29. RESULTS
148 156 archaeal taxonomy_domain With respect to understanding the RAD51:RAD51 interaction, no human crystal structure has been published, however, several oligomeric structures of archaeal RadA as well that of Saccharomyces cerevisiae RAD51 have been reported 27, 28, 29. RESULTS
157 161 RadA protein With respect to understanding the RAD51:RAD51 interaction, no human crystal structure has been published, however, several oligomeric structures of archaeal RadA as well that of Saccharomyces cerevisiae RAD51 have been reported 27, 28, 29. RESULTS
178 202 Saccharomyces cerevisiae species With respect to understanding the RAD51:RAD51 interaction, no human crystal structure has been published, however, several oligomeric structures of archaeal RadA as well that of Saccharomyces cerevisiae RAD51 have been reported 27, 28, 29. RESULTS
203 208 RAD51 protein With respect to understanding the RAD51:RAD51 interaction, no human crystal structure has been published, however, several oligomeric structures of archaeal RadA as well that of Saccharomyces cerevisiae RAD51 have been reported 27, 28, 29. RESULTS
35 39 FxxA structure_element Figure 3B shows a highlight of the FxxA portion of oligomerisation peptide from the S. cerevisiae RAD51 structure, with residues in parentheses corresponding to the human RAD51 protein. RESULTS
51 74 oligomerisation peptide structure_element Figure 3B shows a highlight of the FxxA portion of oligomerisation peptide from the S. cerevisiae RAD51 structure, with residues in parentheses corresponding to the human RAD51 protein. RESULTS
84 97 S. cerevisiae species Figure 3B shows a highlight of the FxxA portion of oligomerisation peptide from the S. cerevisiae RAD51 structure, with residues in parentheses corresponding to the human RAD51 protein. RESULTS
98 103 RAD51 protein Figure 3B shows a highlight of the FxxA portion of oligomerisation peptide from the S. cerevisiae RAD51 structure, with residues in parentheses corresponding to the human RAD51 protein. RESULTS
104 113 structure evidence Figure 3B shows a highlight of the FxxA portion of oligomerisation peptide from the S. cerevisiae RAD51 structure, with residues in parentheses corresponding to the human RAD51 protein. RESULTS
165 170 human species Figure 3B shows a highlight of the FxxA portion of oligomerisation peptide from the S. cerevisiae RAD51 structure, with residues in parentheses corresponding to the human RAD51 protein. RESULTS
171 176 RAD51 protein Figure 3B shows a highlight of the FxxA portion of oligomerisation peptide from the S. cerevisiae RAD51 structure, with residues in parentheses corresponding to the human RAD51 protein. RESULTS
4 13 conserved protein_state The conserved threonine residue at the third position forms a hydrogen bond with the peptide backbone amide, which forms the base of an α‐helix. RESULTS
14 23 threonine residue_name The conserved threonine residue at the third position forms a hydrogen bond with the peptide backbone amide, which forms the base of an α‐helix. RESULTS
62 75 hydrogen bond bond_interaction The conserved threonine residue at the third position forms a hydrogen bond with the peptide backbone amide, which forms the base of an α‐helix. RESULTS
136 143 α‐helix structure_element The conserved threonine residue at the third position forms a hydrogen bond with the peptide backbone amide, which forms the base of an α‐helix. RESULTS
60 69 threonine residue_name In both structural contexts, the role of the third position threonine in FxxA seems to be in stabilising secondary structure; a β‐turn in the case of BRC binding and an α‐helix in the case of RAD51 oligomerisation. RESULTS
73 77 FxxA structure_element In both structural contexts, the role of the third position threonine in FxxA seems to be in stabilising secondary structure; a β‐turn in the case of BRC binding and an α‐helix in the case of RAD51 oligomerisation. RESULTS
128 134 β‐turn structure_element In both structural contexts, the role of the third position threonine in FxxA seems to be in stabilising secondary structure; a β‐turn in the case of BRC binding and an α‐helix in the case of RAD51 oligomerisation. RESULTS
150 153 BRC structure_element In both structural contexts, the role of the third position threonine in FxxA seems to be in stabilising secondary structure; a β‐turn in the case of BRC binding and an α‐helix in the case of RAD51 oligomerisation. RESULTS
169 176 α‐helix structure_element In both structural contexts, the role of the third position threonine in FxxA seems to be in stabilising secondary structure; a β‐turn in the case of BRC binding and an α‐helix in the case of RAD51 oligomerisation. RESULTS
192 197 RAD51 protein In both structural contexts, the role of the third position threonine in FxxA seems to be in stabilising secondary structure; a β‐turn in the case of BRC binding and an α‐helix in the case of RAD51 oligomerisation. RESULTS
7 19 tetrapeptide chemical In the tetrapeptide context these secondary interactions are not present and mutation of threonine to alanine would be expected to have little effect on affinity. RESULTS
77 85 mutation experimental_method In the tetrapeptide context these secondary interactions are not present and mutation of threonine to alanine would be expected to have little effect on affinity. RESULTS
89 98 threonine residue_name In the tetrapeptide context these secondary interactions are not present and mutation of threonine to alanine would be expected to have little effect on affinity. RESULTS
102 109 alanine residue_name In the tetrapeptide context these secondary interactions are not present and mutation of threonine to alanine would be expected to have little effect on affinity. RESULTS
153 161 affinity evidence In the tetrapeptide context these secondary interactions are not present and mutation of threonine to alanine would be expected to have little effect on affinity. RESULTS
69 85 peptide affinity evidence In line with this, although we observe a slight twofold weakening of peptide affinity, the effect is far from being as drastic or inactivating as reported in longer peptide backgrounds 3. It would be interesting to investigate the importance of this residue in the context of the BRC4 peptide, and the oligomerisation peptide. RESULTS
280 284 BRC4 chemical In line with this, although we observe a slight twofold weakening of peptide affinity, the effect is far from being as drastic or inactivating as reported in longer peptide backgrounds 3. It would be interesting to investigate the importance of this residue in the context of the BRC4 peptide, and the oligomerisation peptide. RESULTS
302 325 oligomerisation peptide structure_element In line with this, although we observe a slight twofold weakening of peptide affinity, the effect is far from being as drastic or inactivating as reported in longer peptide backgrounds 3. It would be interesting to investigate the importance of this residue in the context of the BRC4 peptide, and the oligomerisation peptide. RESULTS
28 35 alanine residue_name Rather than indifference to alanine mutation, a significant effect, via lack of secondary structure stabilisation, would be predicted, as indeed has been reported for BRC3 3. RESULTS
36 44 mutation experimental_method Rather than indifference to alanine mutation, a significant effect, via lack of secondary structure stabilisation, would be predicted, as indeed has been reported for BRC3 3. RESULTS
167 171 BRC3 chemical Rather than indifference to alanine mutation, a significant effect, via lack of secondary structure stabilisation, would be predicted, as indeed has been reported for BRC3 3. RESULTS
20 24 FxxA structure_element Two residues in the FxxA motif, phenylalanine and alanine, are highly conserved (Fig 4a). CONCL
32 45 phenylalanine residue_name Two residues in the FxxA motif, phenylalanine and alanine, are highly conserved (Fig 4a). CONCL
50 57 alanine residue_name Two residues in the FxxA motif, phenylalanine and alanine, are highly conserved (Fig 4a). CONCL
63 79 highly conserved protein_state Two residues in the FxxA motif, phenylalanine and alanine, are highly conserved (Fig 4a). CONCL
0 13 Phenylalanine residue_name Phenylalanine mutated to tryptophan, in the context of the tetrapeptide improved potency, contrary to the reported result of comparable activity in the context of BRC4 12. CONCL
14 24 mutated to experimental_method Phenylalanine mutated to tryptophan, in the context of the tetrapeptide improved potency, contrary to the reported result of comparable activity in the context of BRC4 12. CONCL
25 35 tryptophan residue_name Phenylalanine mutated to tryptophan, in the context of the tetrapeptide improved potency, contrary to the reported result of comparable activity in the context of BRC4 12. CONCL
59 71 tetrapeptide chemical Phenylalanine mutated to tryptophan, in the context of the tetrapeptide improved potency, contrary to the reported result of comparable activity in the context of BRC4 12. CONCL
163 167 BRC4 chemical Phenylalanine mutated to tryptophan, in the context of the tetrapeptide improved potency, contrary to the reported result of comparable activity in the context of BRC4 12. CONCL
0 7 Proline residue_name Proline at the third position similarly improved potency. CONCL
21 29 mutating experimental_method Activity was lost by mutating the terminal alanine to glycine, but recovered somewhat with the novel α‐amino butyric acid (U). CONCL
43 50 alanine residue_name Activity was lost by mutating the terminal alanine to glycine, but recovered somewhat with the novel α‐amino butyric acid (U). CONCL
54 61 glycine residue_name Activity was lost by mutating the terminal alanine to glycine, but recovered somewhat with the novel α‐amino butyric acid (U). CONCL
101 121 α‐amino butyric acid chemical Activity was lost by mutating the terminal alanine to glycine, but recovered somewhat with the novel α‐amino butyric acid (U). CONCL
123 124 U chemical Activity was lost by mutating the terminal alanine to glycine, but recovered somewhat with the novel α‐amino butyric acid (U). CONCL
0 9 Threonine residue_name Threonine was found to be relatively unimportant in the tetrapeptides but has been previously reported to be crucial in the context of BRC3. CONCL
56 69 tetrapeptides chemical Threonine was found to be relatively unimportant in the tetrapeptides but has been previously reported to be crucial in the context of BRC3. CONCL
135 139 BRC3 chemical Threonine was found to be relatively unimportant in the tetrapeptides but has been previously reported to be crucial in the context of BRC3. CONCL
58 67 threonine residue_name The reason for this disconnection is suggested to be that threonine plays a role in stabilising the β‐turn in the BRC repeats, which is absent in the tetrapeptides studied. CONCL
100 106 β‐turn structure_element The reason for this disconnection is suggested to be that threonine plays a role in stabilising the β‐turn in the BRC repeats, which is absent in the tetrapeptides studied. CONCL
114 125 BRC repeats structure_element The reason for this disconnection is suggested to be that threonine plays a role in stabilising the β‐turn in the BRC repeats, which is absent in the tetrapeptides studied. CONCL
150 163 tetrapeptides chemical The reason for this disconnection is suggested to be that threonine plays a role in stabilising the β‐turn in the BRC repeats, which is absent in the tetrapeptides studied. CONCL
46 54 hot‐spot site This may lead to a more general caution, that hot‐spot data should be interpreted by considering the bound interaction with the protein, as well as the potential role in stabilising the bound peptide secondary structure. CONCL
78 106 alanine‐scanning experiments experimental_method In either case, the requirement for structural data in correctly interpreting alanine‐scanning experiments is reinforced. CONCL
32 36 FxxA structure_element Summary of key observations (A) FxxA motif sequence conservation of Rad51 oligomerisation sequences and BRC repeats. (B) Highlight of SAR identified for the tetrapeptide. FIG
68 73 Rad51 protein Summary of key observations (A) FxxA motif sequence conservation of Rad51 oligomerisation sequences and BRC repeats. (B) Highlight of SAR identified for the tetrapeptide. FIG
104 115 BRC repeats structure_element Summary of key observations (A) FxxA motif sequence conservation of Rad51 oligomerisation sequences and BRC repeats. (B) Highlight of SAR identified for the tetrapeptide. FIG
157 169 tetrapeptide chemical Summary of key observations (A) FxxA motif sequence conservation of Rad51 oligomerisation sequences and BRC repeats. (B) Highlight of SAR identified for the tetrapeptide. FIG
19 21 ΔG evidence The differences in ΔG for different peptide variants relative to FHTA are shown in the bar chart with colouring matching with the structural overlay below. (C) Overlay of tetrapeptide structures, with wild‐type FHTA peptide across the figure for reference and truncated segments of mutated residues shown in each panel. FIG
65 69 FHTA structure_element The differences in ΔG for different peptide variants relative to FHTA are shown in the bar chart with colouring matching with the structural overlay below. (C) Overlay of tetrapeptide structures, with wild‐type FHTA peptide across the figure for reference and truncated segments of mutated residues shown in each panel. FIG
130 148 structural overlay experimental_method The differences in ΔG for different peptide variants relative to FHTA are shown in the bar chart with colouring matching with the structural overlay below. (C) Overlay of tetrapeptide structures, with wild‐type FHTA peptide across the figure for reference and truncated segments of mutated residues shown in each panel. FIG
160 167 Overlay experimental_method The differences in ΔG for different peptide variants relative to FHTA are shown in the bar chart with colouring matching with the structural overlay below. (C) Overlay of tetrapeptide structures, with wild‐type FHTA peptide across the figure for reference and truncated segments of mutated residues shown in each panel. FIG
171 183 tetrapeptide chemical The differences in ΔG for different peptide variants relative to FHTA are shown in the bar chart with colouring matching with the structural overlay below. (C) Overlay of tetrapeptide structures, with wild‐type FHTA peptide across the figure for reference and truncated segments of mutated residues shown in each panel. FIG
184 194 structures evidence The differences in ΔG for different peptide variants relative to FHTA are shown in the bar chart with colouring matching with the structural overlay below. (C) Overlay of tetrapeptide structures, with wild‐type FHTA peptide across the figure for reference and truncated segments of mutated residues shown in each panel. FIG
201 210 wild‐type protein_state The differences in ΔG for different peptide variants relative to FHTA are shown in the bar chart with colouring matching with the structural overlay below. (C) Overlay of tetrapeptide structures, with wild‐type FHTA peptide across the figure for reference and truncated segments of mutated residues shown in each panel. FIG
211 215 FHTA structure_element The differences in ΔG for different peptide variants relative to FHTA are shown in the bar chart with colouring matching with the structural overlay below. (C) Overlay of tetrapeptide structures, with wild‐type FHTA peptide across the figure for reference and truncated segments of mutated residues shown in each panel. FIG
17 21 WHTA structure_element Purple carbon is WHTA, light blue is FATA, yellow is FHPA, cyan is FHTG and grey carbon is FHTA. FIG
37 41 FATA structure_element Purple carbon is WHTA, light blue is FATA, yellow is FHPA, cyan is FHTG and grey carbon is FHTA. FIG
53 57 FHPA structure_element Purple carbon is WHTA, light blue is FATA, yellow is FHPA, cyan is FHTG and grey carbon is FHTA. FIG
67 71 FHTG structure_element Purple carbon is WHTA, light blue is FATA, yellow is FHPA, cyan is FHTG and grey carbon is FHTA. FIG
91 95 FHTA structure_element Purple carbon is WHTA, light blue is FATA, yellow is FHPA, cyan is FHTG and grey carbon is FHTA. FIG
46 50 FHTG structure_element Note the C‐terminal amide changes position in FHTG without the anchoring methyl group. FIG
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