Biochemistry and genetics of eukaryotic mismatch repair.

Kolodner, Richard D.

doi:10.1101/gad.10.12.1433

Cited by 556 publications

(422 citation statements)

References 76 publications

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“…These genes encode proteins, which are homologues of the bacterial post replicative DNA mismatch repair (MMR) proteins MutS and MutL. Mutations in the human hMSH2 (mutS homologue) and hMLH1 (mutL homologue) are among the most commonly found mutations in HNPCC (reviewed by Kolodner, 1996). Mutations in these genes lead to a signi®cantly higher mutation rate and MMR defective cells rapidly acquire mutations throughout their genome.…”

Section: Mouse Models For Hnpccmentioning

confidence: 99%

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Mouse models for colorectal cancer

et al. 1999

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Section: Mouse Models For Hnpccmentioning

confidence: 99%

“…The mismatch repair system in eukaryotes is more complex, and several mutS and mutL homologues have Figure 2 Model for eukaryotic mismatch repair been found (reviewed in Kolodner, 1996;Modrich and Lahue, 1996). Genetic studies in S. cerevisisae led to the identi®cation of six mutS homologues.…”

Section: Mouse Models For Hnpccmentioning

confidence: 99%

Mouse models for colorectal cancer

et al. 1999

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“…Subsequently, a characteristic frameshift mutation in the TGF-b RII gene was recognized in a large portion of colon cancer specimens obtained from patients with the hereditary nonpolyposis colon cancer (HNPCC) syndrome Myero et al, 1995;Parsons et al, 1995). However, a strong correlation between TGF-b RII mutation and microsatellite instability has been demonstrated, only for colon and gastric cancers (Eshleman and Markowitz, 1995;Kolodner, 1996;Markowitz et al, 1995;Modrich and Lahue, 1996;Myero et al, 1995;Parsons et al, 1995). Since then, defective expression of TGF-b RII has been demonstrated in gastric, colon, small-cell lung, breast, endometrial, hepatocellular, bladder, and squamous cell cancers as well as retinoblastoma, pheochromocytoma, osteosarcoma, and lymphomas (Chang et al, 1997;Garrigue-Antar et al, 1995;Inagaki et al, 1993;Kadin et al, 1994;Kim and Kim, 1996;Kimchi et al, 1988;Park et al, 1994;Markowitz et al, 1995;Markowitz and Roberts, 1996;Sun et al, 1994;Wang et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Transcriptional repression of the transforming growth factor-β type I receptor gene by DNA methylation results in the development of TGF-β resistance in human gastric cancer

et al. 1999

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The transforming growth factor-b (TGF-b) signaling pathway subserves an essential tumor suppressor function in various cell types. A heteromeric complex composed of TGF-b type I (RI) and type II (RII) receptors is required for TGF-b signaling. We have identi®ed a subset of human gastric cancer cell lines which are insensitive to TGF-b and which express a low level of TGF-b type I receptor mRNA relative to a gastric cancer cell line which is highly responsive to TGF-b. Using these cells, we show that hypermethylation of a CpG island in the 5' region of the TGF-b RI gene provides another potentially important mechanism of escape from negative growth control by TGF-b. This hypermethylation was found in four of ®ve human gastric cancer cell lines and ®ve out of 40 (12.5%) primary tumors examined. In human gastric cancer cell lines, treatment with the demethylating agent, 5-aza-2'-deoxycytidine, resulted in increased expression of the TGF-b RI gene, but not the RII gene. Transient transfection of an RI expression vector into the TGF-b resistant SNU-601 cell line restores TGF-b responsiveness. These ®ndings suggest that one of the mechanisms of escape from autocrine or paracrine growth control by TGF-b during carcinogenesis could involve aberrant methylation of CpG islands in the 5' region of the TGF-b RI gene.

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“…The human mismatch repair system plays an important role in maintaining genomic integrity by removing replication errors from DNA in a strand-speci®c manner (Eshleman and Markowitz, 1996;Kolodner, 1996;Marra and Boland, 1995;Modrich, 1997). Inactivation of this DNA repair system raises mutation rate by two to three orders of magnitude (Bhattacharyya et al, 1994;Eshleman et al, 1995), and leads to the development of human cancers with microsatellite instability (Eshleman and Markowitz, 1996;Fishel and Kolodner, 1995;Kinzler and Vogelstein, 1996;Marra and Boland, 1995).…”

Section: Introductionmentioning

confidence: 99%

“…The human mismatch repair system involves interaction of several proteins including hMSH2, hMSH3, hMSH6, hMLH1, hPMS2, and possibly hPMS1 (Kolodner, 1996;Modrich and Lahue, 1996). Of these, germ line mutations in hMSH2 and hMLH1 account for the great majority of HNPCC kindreds (Kinzler and Vogelstein, 1996;Peltomaki and Vasen, 1997); and somatic inactivation of hMLH1, hMSH2, hMSH3 and hMSH6 has been demonstrated in various sporadic colon cancers Malkhosyan et al, 1996;Risinger et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Somatic mutation of hPMS2 as a possible cause of sporadic human colon cancer with microsatellite instability

Xia

Littman

et al. 2000

Oncogene

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Inactivation of DNA-mismatch repair underlies the genesis of microsatellite unstable (MSI) colon cancers. hPMS2 is one of several genes encoding components of the DNA-mismatch repair complex, and germline hPMS2 mutations have been found in a few kindreds with hereditary nonpolyposis colorectal carcinoma (HNPCC), in whom hereditary MSI colon cancers develop. However, mice bearing null hPMS2 genes do not develop colon cancers and hPMS2 mutations in sporadic human colon cancers have not been described. Here we report that in Vaco481 colon cancer the hPMS2 gene is inactivated by somatic mutations of both hPMS2 alleles. The cell line derived from this tumor is functionally de®cient in DNA mismatch repair. This de®ciency can be biochemically complemented by addition of a puri®ed hMLH1-hPMS2 (hMutLa) complex. The hPMS2 de®cient Vaco481 cancer cell line demonstrates microsatellite instability, an elevated HPRT gene mutation rate, and resistance to the cytotoxicity of the alkylator MNNG. We conclude that somatic inactivation of hPMS2 can play a role in development of sporadic MSI colon cancer expressing the full range of cancer phenotypes associated with inactivation of the mismatch repair system. Oncogene (2000) 19, 2249 ± 2256.

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Biochemistry and genetics of eukaryotic mismatch repair.

Cited by 556 publications

References 76 publications

Mouse models for colorectal cancer

Mouse models for colorectal cancer

Transcriptional repression of the transforming growth factor-β type I receptor gene by DNA methylation results in the development of TGF-β resistance in human gastric cancer

Somatic mutation of hPMS2 as a possible cause of sporadic human colon cancer with microsatellite instability

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