Protein: DNA mismatch repair protein MSH6 (MutS protein homolog 6) (Postmeiotic segregation protein 3) (Q03834)
Organism: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Function: Component of the post-replicative DNA mismatch repair system (MMR). Heterodimerizes with MSH2 to form MutS alpha, which binds to DNA mismatches thereby initiating DNA repair. MSH6 provides substrate-binding and substrate specificity to the complex. When bound, MutS alpha bends the DNA helix and shields approximately 20 base pairs. Acts mainly to repair base-base and single insertion-deletion mismatches that occur during replication, but can also repair longer insertion-deletion loops (IDLs), although with decreasing efficiency as the size of the extrahelical loop increases. After mismatch binding, forms a ternary complex with the MutL alpha heterodimer, which is thought to be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis. ATP binding and hydrolysis by the MutS alpha complex is crucial for MMR. Both subunits bind ATP, but with differing affinities, and their ATPase kinetics are also very different. MSH6 binds and hydrolyzes ATP rapidly, whereas MSH2 catalyzes ATP at a substantially slower rate. Binding to a mismatched base pair suppresses MSH6-catalyzed ATP hydrolysis, but not the activity of MSH2. ATP binding to both subunits is necessary to trigger a change in MutS alpha interaction with mismatched DNA, converting MutS alpha into a sliding clamp capable of hydrolysis-independent movement along DNA, and also facilitates formation of ternary complexes containing MutS and MutL proteins and the mismatch. May also be involved in resolution of recombination intermediates.
Subcellular location: Nucleus {ECO:0000269|PubMed:14562095}.
Interaction partners:
- DNA mismatch repair protein PMS1
- DNA mismatch repair protein MSH3
- DNA mismatch repair protein MSH2
- Proliferating cell nuclear antigen
- DNA mismatch repair protein MLH1
- DNA mismatch repair protein MLH3
- Exodeoxyribonuclease 1
- DNA polymerase delta catalytic subunit
- DNA polymerase epsilon catalytic subunit A
- DNA repair and recombination protein RAD52
Sequence:
MAPATPKTSKTAHFENGSTSSQKKMKQSSLLSFFSKQVPSGTPSKKVQKPTPATLENTATDKITKNPQGGKTGKLFVDVDEDNDLTIAEETVSTVRSDIMHSQEPQSDTMLNSNTTEPKSTTTDEDLSSSQSRRNHKRRVNYAESDDDDSDTTFTAKRKKGKVVDSESDEDEYLPDKNDGDEDDDIADDKEDIKGELAEDSGDDDDLISLAETTSKKKFSYNTSHSSSPFTRNISRDNSKKKSRPNQAPSRSYNPSHSQPSATSKSSKFNKQNEERYQWLVDERDAQRRPKSDPEYDPRTLYIPSSAWNKFTPFEKQYWEIKSKMWDCIVFFKKGKFFELYEKDALLANALFDLKIAGGGRANMQLAGIPEMSFEYWAAQFIQMGYKVAKVDQRESMLAKEMREGSKGIVKRELQCILTSGTLTDGDMLHSDLATFCLAIREEPGNFYNETQLDSSTIVQKLNTKIFGAAFIDTATGELQMLEFEDDSECTKLDTLMSQVRPMEVVMERNNLSTLANKIVKFNSAPNAIFNEVKAGEEFYDCDKTYAEIISSEYFSTEEDWPEVLKSYYDTGKKVGFSAFGGLLYYLKWLKLDKNLISMKNIKEYDFVKSQHSMVLDGITLQNLEIFSNSFDGSDKGTLFKLFNRAITPMGKRMMKKWLMHPLLRKNDIESRLDSVDSLLQDITLREQLEITFSKLPDLERMLARIHSRTIKVKDFEKVITAFETIIELQDSLKNNDLKGDVSKYISSFPEGLVEAVKSWTNAFERQKAINENIIVPQRGFDIEFDKSMDRIQELEDELMEILMTYRKQFKCSNIQYKDSGKEIYTIEIPISATKNVPSNWVQMAANKTYKRYYSDEVRALARSMAEAKEIHKTLEEDLKNRLCQKFDAHYNTIWMPTIQAISNIDCLLAITRTSEYLGAPSCRPTIVDEVDSKTNTQLNGFLKFKSLRHPCFNLGATTAKDFIPNDIELGKEQPRLGLLTGANAAGKSTILRMACIAVIMAQMGCYVPCESAVLTPIDRIMTRLGANDNIMQGKSTFFVELAETKKILDMATNRSLLVVDELGRGGSSSDGFAIAESVLHHVATHIQSLGFFATHYGTLASSFKHHPQVRPLKMSILVDEATRNVTFLYKMLEGQSEGSFGMHVASMCGISKEIIDNAQIAADNLEHTSRLVKERDLAANNLNGEVVSVPGGLQSDFVRIAYGDGLKNTKLGSGEGVLNYDWNIKRNVLKSLFSIIDDLQS