Protein: DNA mismatch repair protein MSH2 (MutS protein homolog 2) (P25847)
Organism: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Function: Component of the post-replicative DNA mismatch repair system (MMR). Forms two different heterodimers: MutS alpha (MSH2-MSH6 heterodimer) and MutS beta (MSH2-MSH3 heterodimer), which bind to DNA mismatches thereby initiating DNA repair. MSH2 seems to act as a scaffold for the other MutS homologs that provide substrate-binding and substrate specificity. When bound, heterodimers bend the DNA helix and shield approximately 20 base pairs. MutS alpha 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. MutS beta acts mainly to repair IDLs from 2 to 13 nucleotides in size, but can also repair base-base and single insertion-deletion mismatches. After mismatch binding, MutS alpha or beta form a ternary complex with a MutL heterodimer, which is thought to be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis. ATP binding and hydrolysis play a pivotal role in mismatch repair functions. 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. MutS beta also has a role in regulation of heteroduplex formation during mitotic and meiotic recombination. MutS beta binds to DNA flap structures predicted to form during recombination, and is required for 3' non-homologous tail removal (NHTR). MutS beta-binding alters the DNA conformation of its substrate at the ds/ssDNA junction and may facilitate its recognition and/or cleavage by the downstream nucleotide excision repair (NER) RAD1-RAD10 endonuclease.
Subcellular location: Nucleus {ECO:0000269|PubMed:14562095}.
Interaction partners:
- DNA mismatch repair protein PMS1
- DNA mismatch repair protein MSH6
- Exodeoxyribonuclease 1
- DNA mismatch repair protein MSH3
- DNA mismatch repair protein MLH1
- DNA mismatch repair protein MLH3
- DNA repair protein RAD1
- DNA repair protein RAD10
- Proliferating cell nuclear antigen
- DNA polymerase delta catalytic subunit
Sequence:
MSSTRPELKFSDVSEERNFYKKYTGLPKKPLKTIRLVDKGDYYTVIGSDAIFVADSVYHTQSVLKNCQLDPVTAKNFHEPTKYVTVSLQVLATLLKLCLLDLGYKVEIYDKGWKLIKSASPGNIEQVNELMNMNIDSSIIIASLKVQWNSQDGNCIIGVAFIDTTAYKVGMLDIVDNEVYSNLESFLIQLGVKECLVQDLTSNSNSNAEMQKVINVIDRCGCVVTLLKNSEFSEKDVELDLTKLLGDDLALSLPQKYSKLSMGACNALIGYLQLLSEQDQVGKYELVEHKLKEFMKLDASAIKALNLFPQGPQNPFGSNNLAVSGFTSAGNSGKVTSLFQLLNHCKTNAGVRLLNEWLKQPLTNIDEINKRHDLVDYLIDQIELRQMLTSEYLPMIPDIRRLTKKLNKRGNLEDVLKIYQFSKRIPEIVQVFTSFLEDDSPTEPVNELVRSVWLAPLSHHVEPLSKFEEMVETTVDLDAYEENNEFMIKVEFNEELGKIRSKLDTLRDEIHSIHLDSAEDLGFDPDKKLKLENHHLHGWCMRLTRNDAKELRKHKKYIELSTVKAGIFFSTKQLKSIANETNILQKEYDKQQSALVREIINITLTYTPVFEKLSLVLAHLDVIASFAHTSSYAPIPYIRPKLHPMDSERRTHLISSRHPVLEMQDDISFISNDVTLESGKGDFLIITGPNMGGKSTYIRQVGVISLMAQIGCFVPCEEAEIAIVDAILCRVGAGDSQLKGVSTFMVEILETASILKNASKNSLIIVDELGRGTSTYDGFGLAWAIAEHIASKIGCFALFATHFHELTELSEKLPNVKNMHVVAHIEKNLKEQKHDDEDITLLYKVEPGISDQSFGIHVAEVVQFPEKIVKMAKRKANELDDLKTNNEDLKKAKLSLQEVNEGNIRLKALLKEWIRKVKEEGLHDPSKITEEASQHKIQELLRAIANEPEKENDNYLKYIKALLL