MSH2

MutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli)
PDB rendering based on 2o8b.
Available structures PDB 2O8B, 2O8C, 2O8D, 2O8E, 2O8F
Identifiers
Symbols	MSH2; COCA1; FCC1; HNPCC; HNPCC1; LCFS2
External IDs	OMIM: 609309 MGI: 101816 HomoloGene: 210 GeneCards: MSH2 Gene
Gene Ontology Molecular function • nucleotide binding • magnesium ion binding • four-way junction DNA binding • Y-form DNA binding • loop DNA binding • double-strand/single-strand DNA junction binding • DNA binding • damaged DNA binding • double-stranded DNA binding • single-stranded DNA binding • protein binding • protein binding • ATP binding • protein C-terminus binding • DNA-dependent ATPase activity • ATPase activity • centromeric DNA binding • enzyme binding • protein kinase binding • mismatched DNA binding • guanine/thymine mispair binding • guanine/thymine mispair binding • dinucleotide insertion or deletion binding • single guanine insertion binding • single thymine insertion binding • dinucleotide repeat insertion binding • oxidized purine DNA binding • MutLalpha complex binding • identical protein binding • protein homodimerization activity • ADP binding Cellular component • nuclear chromosome • nucleus • MutSalpha complex • MutSbeta complex Biological process • meiotic mismatch repair • in utero embryonic development • oxidative phosphorylation • ATP catabolic process • DNA repair • mismatch repair • postreplication repair • double-strand break repair • meiotic gene conversion • cell cycle arrest • germ cell development • spermatogenesis • determination of adult lifespan • male gonad development • response to X-ray • response to X-ray • response to UV-B • response to UV-B • response to organic cyclic compound • somatic hypermutation of immunoglobulin genes • somatic recombination of immunoglobulin gene segments • B cell mediated immunity • B cell differentiation • intra-S DNA damage checkpoint • response to drug • DNA damage response, signal transduction by p53 class mediator resulting in induction of apoptosis • response to amino acid stimulus • negative regulation of neuron apoptosis • maintenance of DNA repeat elements • negative regulation of reciprocal meiotic recombination • isotype switching • isotype switching • negative regulation of DNA recombination • negative regulation of DNA recombination • positive regulation of helicase activity Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	4436	17685
Ensembl	ENSG00000095002	ENSMUSG00000024151
UniProt	P43246	Q3TZI5
RefSeq (mRNA)	NM_000251.1	NM_008628.2
RefSeq (protein)	NP_000242.1	NP_032654.1
Location (UCSC)	Chr 2: 47.63 – 47.79 Mb	Chr 17: 88.07 – 88.12 Mb
PubMed search	[1]	[2]

MSH2 is a gene commonly associated with Hereditary nonpolyposis colorectal cancer.

MSH2 was identified as a locus frequently mutated in hereditary nonpolyposis colon cancer (HNPCC). When cloned, it was discovered to be a human homolog of the E. coli mismatch repair gene mutS, consistent with the characteristic alterations in microsatellite sequences (RER+ phenotype) found in HNPCC.^[1] It is also associated with some endometrial cancers.

Interactions

MSH2 has been shown to interact with Exonuclease 1,^[2][3][4] MSH3,^[5][6][7][8] MSH6,^{[9][5][6][7][8]} CHEK2,^[10][11] MAX,^[12] Ataxia telangiectasia and Rad3 related^[5] and BRCA1.^[13][9]

References

1. ^ "Entrez Gene: MSH2 mutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4436. 
2. ^ Rasmussen, L J; Rasmussen M, Lee B, Rasmussen A K, Wilson D M, Nielsen F C, Bisgaard H C (Jun. 2000). "Identification of factors interacting with hMSH2 in the fetal liver utilizing the yeast two-hybrid system. In vivo interaction through the C-terminal domains of hEXO1 and hMSH2 and comparative expression analysis". Mutat. Res. (NETHERLANDS) 460 (1): 41–52. doi:10.1016/S0921-8777(00)00012-4. ISSN 0027-5107. PMID 10856833. 
3. ^ Schmutte, C; Marinescu R C, Sadoff M M, Guerrette S, Overhauser J, Fishel R (Oct. 1998). "Human exonuclease I interacts with the mismatch repair protein hMSH2". Cancer Res. (UNITED STATES) 58 (20): 4537–42. ISSN 0008-5472. PMID 9788596. 
4. ^ Schmutte, C; Sadoff M M, Shim K S, Acharya S, Fishel R (Aug. 2001). "The interaction of DNA mismatch repair proteins with human exonuclease I". J. Biol. Chem. (United States) 276 (35): 33011–8. doi:10.1074/jbc.M102670200. ISSN 0021-9258. PMID 11427529. 
5. ^ ^{a b c} Wang, Yi; Qin Jun (Dec. 2003). "MSH2 and ATR form a signaling module and regulate two branches of the damage response to DNA methylation". Proc. Natl. Acad. Sci. U.S.A. (United States) 100 (26): 15387–92. doi:10.1073/pnas.2536810100. ISSN 0027-8424. PMC 307577. PMID 14657349. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=307577. 
6. ^ ^{a b} Guerrette, S; Wilson T, Gradia S, Fishel R (Nov. 1998). "Interactions of human hMSH2 with hMSH3 and hMSH2 with hMSH6: examination of mutations found in hereditary nonpolyposis colorectal cancer". Mol. Cell. Biol. (UNITED STATES) 18 (11): 6616–23. ISSN 0270-7306. PMC 109246. PMID 9774676. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=109246. 
7. ^ ^{a b} Bocker, T; Barusevicius A, Snowden T, Rasio D, Guerrette S, Robbins D, Schmidt C, Burczak J, Croce C M, Copeland T, Kovatich A J, Fishel R (Feb. 1999). "hMSH5: a human MutS homologue that forms a novel heterodimer with hMSH4 and is expressed during spermatogenesis". Cancer Res. (UNITED STATES) 59 (4): 816–22. ISSN 0008-5472. PMID 10029069. 
8. ^ ^{a b} Acharya, S; Wilson T, Gradia S, Kane M F, Guerrette S, Marsischky G T, Kolodner R, Fishel R (Nov. 1996). "hMSH2 forms specific mispair-binding complexes with hMSH3 and hMSH6". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 93 (24): 13629–34. doi:10.1073/pnas.93.24.13629. ISSN 0027-8424. PMC 19374. PMID 8942985. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=19374. 
9. ^ ^{a b} Wang, Y; Cortez D, Yazdi P, Neff N, Elledge S J, Qin J (Apr. 2000). "BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures". Genes Dev. (UNITED STATES) 14 (8): 927–39. ISSN 0890-9369. PMC 316544. PMID 10783165. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=316544. 
10. ^ Adamson, Aaron W; Beardsley Dillon I, Kim Wan-Ju, Gao Yajuan, Baskaran R, Brown Kevin D (Mar. 2005). "Methylator-induced, mismatch repair-dependent G2 arrest is activated through Chk1 and Chk2". Mol. Biol. Cell (United States) 16 (3): 1513–26. doi:10.1091/mbc.E04-02-0089. ISSN 1059-1524. PMC 551512. PMID 15647386. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=551512. 
11. ^ Brown, Kevin D; Rathi Abhilasha, Kamath Ravindra, Beardsley Dillon I, Zhan Qimin, Mannino Jennifer L, Baskaran R (Jan. 2003). "The mismatch repair system is required for S-phase checkpoint activation". Nat. Genet. (United States) 33 (1): 80–4. doi:10.1038/ng1052. ISSN 1061-4036. PMID 12447371. 
12. ^ Mac Partlin, Mary; Homer Elizabeth, Robinson Helen, McCormick Carol J, Crouch Dorothy H, Durant Stephen T, Matheson Elizabeth C, Hall Andrew G, Gillespie David A F, Brown Robert (Feb. 2003). "Interactions of the DNA mismatch repair proteins MLH1 and MSH2 with c-MYC and MAX". Oncogene (England) 22 (6): 819–25. doi:10.1038/sj.onc.1206252. ISSN 0950-9232. PMID 12584560. 
13. ^ Wang, Q; Zhang H, Guerrette S, Chen J, Mazurek A, Wilson T, Slupianek A, Skorski T, Fishel R, Greene M I (Aug. 2001). "Adenosine nucleotide modulates the physical interaction between hMSH2 and BRCA1". Oncogene (England) 20 (34): 4640–9. doi:10.1038/sj.onc.1204625. ISSN 0950-9232. PMID 11498787. 

Further reading

• Jiricny J (1994). "Colon cancer and DNA repair: have mismatches met their match?". Trends Genet. 10 (5): 164–8. doi:10.1016/0168-9525(94)90093-0. PMID 8036718. 
• Fishel R, Wilson T (1997). "MutS homologs in mammalian cells.". Curr. Opin. Genet. Dev. 7 (1): 105–13. doi:10.1016/S0959-437X(97)80117-7. PMID 9024626. 
• Lothe RA (1997). "Microsatellite instability in human solid tumors.". Molecular medicine today 3 (2): 61–8. doi:10.1016/S1357-4310(96)10055-1. PMID 9060003. 
• Peltomäki P, de la Chapelle A (1997). "Mutations predisposing to hereditary nonpolyposis colorectal cancer.". Adv. Cancer Res. 71: 93–119. doi:10.1016/S0065-230X(08)60097-4. PMID 9111864. 
• Papadopoulos N, Lindblom A (1997). "Molecular basis of HNPCC: mutations of MMR genes.". Hum. Mutat. 10 (2): 89–99. doi:10.1002/(SICI)1098-1004(1997)10:2<89::AID-HUMU1>3.0.CO;2-H. PMID 9259192. 
• Kauh J, Umbreit J (2004). "Colorectal cancer prevention.". Current problems in cancer 28 (5): 240–64. doi:10.1016/j.currproblcancer.2004.05.004. PMID 15375803. 
• Warusavitarne J, Schnitzler M (2007). "The role of chemotherapy in microsatellite unstable (MSI-H) colorectal cancer.". International journal of colorectal disease 22 (7): 739–48. doi:10.1007/s00384-006-0228-0. PMID 17109103. 
• Wei Q, Xu X, Cheng L, et al. (1995). "Simultaneous amplification of four DNA repair genes and beta-actin in human lymphocytes by multiplex reverse transcriptase-PCR.". Cancer Res. 55 (21): 5025–9. PMID 7585546. 
• Wilson TM, Ewel A, Duguid JR, et al. (1995). "Differential cellular expression of the human MSH2 repair enzyme in small and large intestine.". Cancer Res. 55 (22): 5146–50. PMID 7585562. 
• Drummond JT, Li GM, Longley MJ, Modrich P (1995). "Isolation of an hMSH2-p160 heterodimer that restores DNA mismatch repair to tumor cells.". Science 268 (5219): 1909–12. doi:10.1126/science.7604264. PMID 7604264. 
• Kolodner RD, Hall NR, Lipford J, et al. (1995). "Structure of the human MSH2 locus and analysis of two Muir-Torre kindreds for msh2 mutations.". Genomics 24 (3): 516–26. doi:10.1006/geno.1994.1661. PMID 7713503. 
• Wijnen J, Vasen H, Khan PM, et al. (1995). "Seven new mutations in hMSH2, an HNPCC gene, identified by denaturing gradient-gel electrophoresis.". Am. J. Hum. Genet. 56 (5): 1060–6. PMC 1801472. PMID 7726159. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1801472. 
• Mary JL, Bishop T, Kolodner R, et al. (1995). "Mutational analysis of the hMSH2 gene reveals a three base pair deletion in a family predisposed to colorectal cancer development.". Hum. Mol. Genet. 3 (11): 2067–9. PMID 7874129. 
• Fishel R, Ewel A, Lescoe MK (1994). "Purified human MSH2 protein binds to DNA containing mismatched nucleotides.". Cancer Res. 54 (21): 5539–42. PMID 7923193. 
• Fishel R, Ewel A, Lee S, et al. (1994). "Binding of mismatched microsatellite DNA sequences by the human MSH2 protein.". Science 266 (5189): 1403–5. doi:10.1126/science.7973733. PMID 7973733. 
• Liu B, Parsons RE, Hamilton SR, et al. (1994). "hMSH2 mutations in hereditary nonpolyposis colorectal cancer kindreds.". Cancer Res. 54 (17): 4590–4. PMID 8062247. 
• Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.". Gene 138 (1-2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298. 
• Fishel R, Lescoe MK, Rao MR, et al. (1994). "The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer.". Cell 77 (1): 167. doi:10.1016/0092-8674(94)90306-9. PMID 8156592. 
• Fishel R, Lescoe MK, Rao MR, et al. (1994). "The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer.". Cell 75 (5): 1027–38. doi:10.1016/0092-8674(93)90546-3. PMID 8252616. 

See also

• Mismatch_repair#MutS

External links

• MeSH MutS+Homolog+2+Protein