Genomic Organization and Expression of the Human MSH3 Gene

Watanabe, Atsushi; Ikejima, Miyoko; Suzuki, Noriko; Shimada, Takashi

doi:10.1006/geno.1996.0053

Cited by 49 publications

(36 citation statements)

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“…References: E. coli MutS-related proteins: Kolodner 1992a, Fishel et al 1993;Leach et al 1993;New et al 1993;Drummond et al 1995;Palombo et al 1995;Marsischky et al 1996;Watanabe et al 1996). E. coli MutL-related proteins: (Bronner et al 1994;Nicolaides et al 1994;Papadopoulos et al 1994;Prolla 1994a,b).…”

Section: Homologs Of the Bacterial Muts Proteinsmentioning

confidence: 99%

Biochemistry and genetics of eukaryotic mismatch repair.

Kolodner¹

1996

Genes Dev.

556

415

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Section: Homologs Of the Bacterial Muts Proteinsmentioning

confidence: 99%

Biochemistry and genetics of eukaryotic mismatch repair.

Kolodner¹

1996

Genes Dev.

556

415

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“…In recent years, the human homologues of the bacterial MMR enzymes have been discovered. To date, eight such genes have been identi®fed in humans, MLH1 (Bronner et al, 1994;Han et al, 1995), MSH2 Fishel et al, 1993;Peltomaki et al, 1993), MSH3 (Fujii and Shimada, 1989;Watanabe et al, 1996), MSH4 (PaquisFlucklinger et al, 1997), MSH5 (Edelmann et al, 1999;Her and Doggett, 1998), MSH6 (Drummond et al, 1995;Palombo et al, 1995;Papadopoulos et al, 1995), PMS1 (Horii et al, 1994;Nicolaides et al, 1994) and PMS2 (Narayanan et al, 1997;Nicolaides et al, 1994), but their mechanisms of action have not yet been fully elucidated. In humans MMR de®ciency was initially associated with the hereditary syndrome HNPCC (Hereditary Non-Polyposis Colorectal Cancer) (de la Chapelle and Peltomaki, 1995), a relatively common genetic condition that a ects 1 : 200 people.…”

Section: Introductionmentioning

confidence: 99%

DNA methylator and mismatch repair phenotypes are not mutually exclusive in colorectal cancer cell lines

et al. 2000

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A potential link between DNA repair and de novo methylation of exogenous sequences in colorectal cancer cell lines suggested that cells de®cient in mismatch repair (MMR 7 ) had an increased ability to silence the introduced virus promoter by DNA methylation due to the presence of a methylator phenotype (MET + ) (Lengauer et al., 1997a). We explored this relationship in more detail and found that although there was a clear di erence in the abilities of MMR + cells to express the viral promoter compared to their MMR 7 counterparts, this di erence was not consistently explained by levels of methylation in the viral promoter. Furthermore, we were unable to distinguish di erences between the levels of methylation of six endogenous known CpG islands or 100 random DNA fragments containing CCGG sites within the cells. No consistent di erences between the abilities of the cells to methylate the CpG island in exon 2 of the p16 gene were observed after transient demethylation by 5-aza-2'-deoxycytidine nor in the levels of expression of three human methyltransferase enzymes. Our results do not therefore support the existence of mutually exclusive DNA methylation (MET) and DNA repair (MMR) phenotypes. Oncogene (2000) 19, 943 ± 952.

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“…The MSH3 R940Q and T1036A polymorphisms encode nonconservative amino acid changes and are located in the C-terminal region, which contains the putative nucleotide binding domain and helix-turn-helix DNAbinding domain. 9 The MSH6 G39E polymorphism resides in exon 1 and encodes a nonconservative amino acid change. The MLH1 I219V polymorphism is located within a conserved residue in exon 8.…”

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confidence: 99%

Mismatch repair polymorphisms and the risk of colorectal cancer

Berndt

Platz

Fallin

et al. 2007

Intl Journal of Cancer

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Rare germline variants in mismatch repair genes have been linked to hereditary nonpolyposis colorectal cancer; however, it is unknown whether common polymorphisms in these genes alter the risk of colorectal cancer. To examine the association between common variants in mismatch repair genes and colorectal cancer, we conducted a case-cohort study within the CLUE II cohort. Four single nucleotide polymorphisms in 3 mismatch repair genes (MSH3 R940Q, MSH3 T1036A, MSH6 G39E and MLH1 I219V) were genotyped in 237 colorectal cancer cases and a subcohort of 2,189 participants. Incidence rate ratios (RRs) and 95% confidence intervals (95% CIs) for each polymorphism were estimated. The MSH3 1036A variant was found to be associated with an increased risk of colorectal cancer (RR 5 1.28, 95% CI: 0.94-1.74 and RR 5 1.65, 95% CI: 1.01-2.70 for the AT and TT genotypes, respectively, with p trend 5 0.02), particularly proximal colon cancer. Although the MSH3 940Q variant was only weakly associated with colorectal cancer overall (p trend 5 0.07), it was associated with a significant increased risk of proximal colon cancer (RR 5 1.69, 95% CI: 1.10-2.61 and RR 5 2.68, 95% CI: 0.96-7.47 for the RQ and QQ genotypes, respectively with p trend 5 0.005). Processed meat intake appeared to modify the association between the MSH3 polymorphisms and colorectal cancer (p interaction < 0.10 for both). No association was observed with the MSH6 and MLH1 polymorphisms overall. This study suggests that common polymorphisms in the mismatch repair gene, MSH3, may increase the risk of colorectal cancer, especially proximal colon cancer. ' 2006 Wiley-Liss, Inc.Key words: mismatch repair; polymorphism; colorectal cancer; DNA repair; meat intake Alterations in mismatch repair are implicated in the etiology of colorectal cancer. Inherited mutations in mismatch repair genes cause hereditary nonpolyposis colorectal cancer (HNPCC), a familial cancer syndrome that accounts for 2-4% of colorectal cancers.1 Individuals with HNPCC inherit an inactivating mutation in a mismatch repair gene (e.g., MSH2, MLH1, MSH6 and PMS2). Although in most cases, the individual only carries one copy of the inactivating mutation and displays normal mismatch repair, 2 the somatic loss of the wild-type allele in the colorectal tissue leads to a dramatic increase in small intragenic mutations, microsatellite instability and the development of colorectal cancer. Nearly all tumors from HNPCC patients display microsatellite instability 3,4 ; however, 10-16% of colorectal tumors from patients without HNPCC also exhibit microsatellite instability, 3,5 suggesting that defects in mismatch repair may also play a role in the etiology of some non-HNPCC colorectal cancers.Mismatch repair primarily corrects single base-pair mismatches and small insertion-deletion loops that arise during replication. In mammals, single base-pair mismatches and single base insertiondeletion loops are recognized by the MSH2-MSH6 heterodimer (MutSa), whereas larger insertion-deletion loops are detected by the MSH...

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Genomic Organization and Expression of the Human MSH3 Gene

Cited by 49 publications

References 0 publications

Biochemistry and genetics of eukaryotic mismatch repair.

Biochemistry and genetics of eukaryotic mismatch repair.

DNA methylator and mismatch repair phenotypes are not mutually exclusive in colorectal cancer cell lines

Mismatch repair polymorphisms and the risk of colorectal cancer

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