| Standard Name | MSH3 |
|---|---|
| Systematic Name | YCR092C |
| Feature Type | ORF, Verified |
| Description | Mismatch repair protein, forms dimers with Msh2p that mediate repair of insertion or deletion mutations and removal of nonhomologous DNA ends, contains a PCNA (Pol30p) binding motif required for genome stability (1, 2 and see Summary Paragraph) |
| Name Description | MutS Homolog |
| Chromosomal Location | |
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| Note: this feature is encoded on the Crick strand. | |
| View Computational GO annotations for MSH3 | |
| Molecular Function | |
| Manually curated | |
| Biological Process | |
| Manually curated | |
| Cellular Component | |
| Manually curated | |
| High-throughput |
| Classical genetics | |
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| null |
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| Large-scale survey | |
| null |
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| Resources |
| 58 total interaction(s) for 33 unique genes/features. | |
| Physical Interactions |
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| Genetic Interactions |
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| Localization | |
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| Phosphorylation | PhosphoGRID | PhosphoPep Database |
| Structure | |
| Homologs |
| Note: this feature is encoded on the Crick strand. | |||||||||||||
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| Last Update | Coordinates: 2011-02-03 | Sequence: 2007-09-06 | ||||||||||||
| Subfeature details |
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| S288C only | |
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| S288C vs. other species | |
| S288C vs. other strains |
| External Links | All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB |
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| Primary SGDID | S000000688 |
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Msh3p functions in conjunction with Msh2p and Msh6p in the mismatch repair (MMR) system, which plays an important role in repairing single-base mismatches and mispaired regions due to small insertions or deletions (3). Genetic and biochemical results suggest that the Msh2p-Msh3p heterodimer has a different substrate specificity than the Msh2p-Msh6p heterodimer (4, 5, 6). The Msh2p-Msh3p heterodimer has a higher affinity for insertion-deletion loops larger than a single nucleotide and does not bind single-base mismatches with high affinity (5, 6, 7).
In addition to their role in mismatch repair, MSH2 and MSH3 are required for the removal of non-homologous DNA and regulation of heteroduplex formation during mitotic and meiotic recombination (1, 8, 9, 10). The Msh2p-Msh3p heterodimer binds double-strand/single-strand DNA junctions, possibly acting as a scaffold to recruit additional DNA repair proteins such as Mlh1p-Pms1p heterodimer or Rad1p-Rad10p heterodimer (11, 6).
Msh3p is one of six E. coli MutS homologs in S. cerevisiae but is more similar to the mouse Rep-3 protein (12). Mutations in the H. sapiens MSH3 protein have been identified in an endometrial carcinoma (OMIM) and in an endometrial carcinoma cell line (13).
| 1) | Sugawara N, et al. (1997) Role of Saccharomyces cerevisiae Msh2 and Msh3 repair proteins in double-strand break-induced recombination. Proc Natl Acad Sci U S A 94(17):9214-9 |
| 2) | Clark AB, et al. (2000) Functional interaction of proliferating cell nuclear antigen with MSH2-MSH6 and MSH2-MSH3 complexes. J Biol Chem 275(47):36498-501 |
| 3) | Harfe BD and Jinks-Robertson S (2000) Mismatch repair proteins and mitotic genome stability. Mutat Res 451(1-2):151-67 |
| 4) | Johnson RE, et al. (1996) Requirement of the yeast MSH3 and MSH6 genes for MSH2-dependent genomic stability. J Biol Chem 271(13):7285-8 |
| 5) | Alani E (1996) The Saccharomyces cerevisiae Msh2 and Msh6 proteins form a complex that specifically binds to duplex oligonucleotides containing mismatched DNA base pairs. Mol Cell Biol 16(10):5604-15 |
| 6) | Surtees JA and Alani E (2006) Mismatch repair factor MSH2-MSH3 binds and alters the conformation of branched DNA structures predicted to form during genetic recombination. J Mol Biol 360(3):523-36 |
| 7) | Habraken Y, et al. (1996) Binding of insertion/deletion DNA mismatches by the heterodimer of yeast mismatch repair proteins MSH2 and MSH3. Curr Biol 6(9):1185-7 |
| 8) | Studamire B, et al. (1999) Separation-of-function mutations in Saccharomyces cerevisiae MSH2 that confer mismatch repair defects but do not affect nonhomologous-tail removal during recombination. Mol Cell Biol 19(11):7558-67 |
| 9) | Chen W and Jinks-Robertson S (1998) Mismatch repair proteins regulate heteroduplex formation during mitotic recombination in yeast. Mol Cell Biol 18(11):6525-37 |
| 10) | Stone JE and Petes TD (2006) Analysis of the proteins involved in the in vivo repair of base-base mismatches and four-base loops formed during meiotic recombination in the yeast Saccharomyces cerevisiae. Genetics 173(3):1223-39 |
| 11) | Habraken Y, et al. (1997) Enhancement of MSH2-MSH3-mediated mismatch recognition by the yeast MLH1-PMS1 complex. Curr Biol 7(10):790-3 |
| 12) | New L, et al. (1993) The yeast gene MSH3 defines a new class of eukaryotic MutS homologues. Mol Gen Genet 239(1-2):97-108 |
| 13) | Risinger JI, et al. (1996) Mutation of MSH3 in endometrial cancer and evidence for its functional role in heteroduplex repair. Nat Genet 14(1):102-5 |





