DNA mismatch repair protein Msh2; hMSH2; mutS protein homolog 2 (MSH2)
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Function
- component of the post-replicative DNA mismatch repair system (MMR)
- all mismatches in DNA base pairs require the MSH2 for repair
- forms two different heterodimers:
- mutS alpha (MSH2-MSH6 heterodimer)
- mutS beta (MSH2-MSH3 heterodimer)
- heterodimers bind to DNA mismatches thus initiating DNA repair
- when bound, heterodimers bend the DNA helix & shield approximately 20 base pairs
- mutS alpha recognizes single base mismatches & dinucleotide insertion-deletion loops (IDL) in the DNA
- mutS beta recognizes larger insertion-deletion loops up to 13 nucleotides long
- after mismatch binding, mutS alpha or beta 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, & resynthesis
- ATP binding & hydrolysis play a pivotal role in mismatch repair functions
- the ATPase activity associated with mutS alpha regulates binding similar to a molecular switch: mismatched DNA provokes ADP-->ATP exchange, resulting in a discernible conformational transition that converts mutS alpha into a sliding clamp capable of hydrolysis-independent diffusion along the DNA backbone
- this transition is crucial for mismatch repair
- mutS alpha may also play a role in DNA homologous recombination repair
- in melanocytes, may modulate both UV-B-induced cell cycle regulation & apoptosis
- phosphorylated by PRKCZ, which may prevent mutS alpha degradation by the ubiquitin-proteasome pathway
- phosphorylated upon DNA damage, probably by ATM or ATR
- heterodimer consisting of MSH2-MSH6 (mutS alpha) or MSH2- MSH3 (mutS beta)
- both heterodimers form a ternary complex with mutL alpha (MLH1-PMS1)
- interacts with EXO1
- part of the BRCA1-associated genome surveillance complex (BASC)
- this association could be a dynamic process changing throughout the cell cycle & within subnuclear domains
- interacts with ATR
- interacts with BTBD12/SLX4; this interaction is direct & links mutS beta to SLX4, a subunit of different structure-specific endonucleases
Structure
belongs to the DNA mismatch repair mutS family
Compartment
Expression
ubiquitously expressed
Pathology
- defects in MSH2 are the cause of
More general terms
Additional terms
- DNA mismatch repair protein Msh6; hMSH6; mutS-alpha 160 kD subunit; p160; G/T mismatch-binding protein; GTMBP; GTBP (MSH6 GTBP)
- DNA mismatch repair; post-replication repair; DNA loop repair
Component of
References
- ↑ UniProt http://www.uniprot.org/uniprot/P43246.html
- ↑ Atlas of Genetics & Cytogenetics in Oncology & Haematology http://atlasgeneticsoncology.org/genes/MSH2ID340ch2p22.html
- ↑ GeneReviews http://www.ncbi.nlm.nih.gov/sites/genetests/lab/gene/MSH2
- ↑ Hereditary non-polyposis colorectal cancer db http://www.nfdht.nl/
- ↑ NIEHS-SNPs http://egp.gs.washington.edu/data/msh2/
- ↑ Karran P. Appropriate partners make good matches. Science. 1995 Jun 30;268(5219):1857-8. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/7604258
Database
- Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=4436
- Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:4436
- OMIM: https://mirror.omim.org/entry/120435
- OMIM: https://mirror.omim.org/entry/158320
- OMIM: https://mirror.omim.org/entry/608089
- OMIM: https://mirror.omim.org/entry/609309
- UniProt: http://www.uniprot.org/uniprot/P43246.html