Protein: DNA endonuclease RBBP8 (EC 3.1.-.-) (CtBP-interacting protein) (CtIP) (Retinoblastoma-binding protein 8) (RBBP-8) (Retinoblastoma-interacting protein and myosin-like) (RIM) (Sporulation in the absence of SPO11 protein 2 homolog) (SAE2) (Q99708)
Organism: Homo sapiens (Human)
Function: Endonuclease that cooperates with the MRE11-RAD50-NBN (MRN) complex in DNA-end resection, the first step of double-strand break (DSB) repair through the homologous recombination (HR) pathway. HR is restricted to S and G2 phases of the cell cycle and preferentially repairs DSBs resulting from replication fork collapse. Key determinant of DSB repair pathway choice, as it commits cells to HR by preventing classical non-homologous end-joining (NHEJ). Functions downstream of the MRN complex and ATM, promotes ATR activation and its recruitment to DSBs in the S/G2 phase facilitating the generation of ssDNA. Component of the BRCA1-RBBP8 complex that regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage. During immunoglobulin heavy chain class-switch recombination, promotes microhomology-mediated alternative end joining (A-NHEJ) and plays an essential role in chromosomal translocations (By similarity).
Subcellular location: Nucleus {ECO:0000269|PubMed:10764811, ECO:0000269|PubMed:17965729, ECO:0000269|PubMed:23623683}. Chromosome {ECO:0000269|PubMed:10764811, ECO:0000269|PubMed:16818604, ECO:0000269|PubMed:27814491, ECO:0000269|PubMed:27889449, ECO:0000269|PubMed:29042561, ECO:0000269|PubMed:33836577}. Note=Associates with sites of DNA damage in S/G2 phase (PubMed:10764811, PubMed:25349192). Recruited to DSBs by the MRE11-RAD50-NBN (MRN) complex following phosphorylation by CDK1, which promotes interaction with NBN (PubMed:27814491, PubMed:27889449, PubMed:33836577). Ubiquitinated RBBP8 binds to chromatin following DNA damage (PubMed:16818604). {ECO:0000269|PubMed:10764811, ECO:0000269|PubMed:16818604, ECO:0000269|PubMed:25349192, ECO:0000269|PubMed:27814491, ECO:0000269|PubMed:27889449, ECO:0000269|PubMed:33836577}.
Interaction partners:
- Breast cancer type 1 susceptibility protein
- DNA repair protein RAD50
- BRCA1-associated RING domain protein 1
- Nibrin
- C-terminal-binding protein 1
- Double-strand break repair protein MRE11
- C-terminal-binding protein 2
- Exonuclease 1
- Zinc finger protein 350
- Breast cancer type 2 susceptibility protein
Sequence:
MNISGSSCGSPNSADTSSDFKDLWTKLKECHDREVQGLQVKVTKLKQERILDAQRLEEFFTKNQQLREQQKVLHETIKVLEDRLRAGLCDRCAVTEEHMRKKQQEFENIRQQNLKLITELMNERNTLQEENKKLSEQLQQKIENDQQHQAAELECEEDVIPDSPITAFSFSGVNRLRRKENPHVRYIEQTHTKLEHSVCANEMRKVSKSSTHPQHNPNENEILVADTYDQSQSPMAKAHGTSSYTPDKSSFNLATVVAETLGLGVQEESETQGPMSPLGDELYHCLEGNHKKQPFEESTRNTEDSLRFSDSTSKTPPQEELPTRVSSPVFGATSSIKSGLDLNTSLSPSLLQPGKKKHLKTLPFSNTCISRLEKTRSKSEDSALFTHHSLGSEVNKIIIQSSNKQILINKNISESLGEQNRTEYGKDSNTDKHLEPLKSLGGRTSKRKKTEEESEHEVSCPQASFDKENAFPFPMDNQFSMNGDCVMDKPLDLSDRFSAIQRQEKSQGSETSKNKFRQVTLYEALKTIPKGFSSSRKASDGNCTLPKDSPGEPCSQECIILQPLNKCSPDNKPSLQIKEENAVFKIPLRPRESLETENVLDDIKSAGSHEPIKIQTRSDHGGCELASVLQLNPCRTGKIKSLQNNQDVSFENIQWSIDPGADLSQYKMDVTVIDTKDGSQSKLGGETVDMDCTLVSETVLLKMKKQEQKGEKSSNEERKMNDSLEDMFDRTTHEEYESCLADSFSQAADEEEELSTATKKLHTHGDKQDKVKQKAFVEPYFKGDERETSLQNFPHIEVVRKKEERRKLLGHTCKECEIYYADMPAEEREKKLASCSRHRFRYIPPNTPENFWEVGFPSTQTCMERGYIKEDLDPCPRPKRRQPYNAIFSPKGKEQKT