DNA mismatch repair

In vitro nifedipine inhibits proliferation of colon cancer cells with a DNA mismatch repair defect that are resistant to 5-fluorouracil. Whether this also... 

MSH2, MLH1, PM SI, DNA mismatch repair enzymes Hereditary nonpolyposis colorectal cancer... 

DNA mismatch repair genes Genes that identify and correct errors in DNA base pairs during DNA replication. Mutations in the mismatch repair genes can lead to cancer by allowing abnormal cells to continue to grow. 

A second group of inherited colon cancers are termed hereditary nonpolyposis colorectal cancer (HNPCC). HNPCC may account for 5% of all colon cancer cases and can be caused by mutations in any of five different genes. All of these genes encode proteins involved in DNA mismatch repair (Fig II-5-3). As with inherited breast cancer, fiiulty DNA repair leads to mutated cells capable of producing tumors. 

Aebi S, Kurdi-Haidar B, Gordon R, Cenni B, Zheng H, Fink D, Christen RD, Boland RC, Koi N, Fishel R, Howell SB (1996) Loss of DNA mismatch repair. in acquired resistance to cisplatin. Cancer Res 56 3087-3090... 

Dean N, McKay R, Miraglia L, Howard R, Cooper S, Giddings ], Nicklin P, Meister L, Ziel R, Geiger T, Muller M, Fabbro D (19 ) Iidiibition of growth of human tumor cell lines in nude mice by an antisense oligonucleotide inhibitor of protein kinase C-a expression. Cancer Res 56 3499-3507 Defranco AL (1991) Immunosuppressants at work. Nature 352 754-755 De las Alas MM, Aebi S, Fink D, Howell SB, Los G (1997) Loss of DNA mismatch repair effects on the rate of mutation to drug resistance. J Natl Cancer Inst 89 1537-1541... 

Martin SA, Hewish M, Sims D et al (2011) Parallel high-throughput RNA interference screens identify PINKl as a potential therapeutic target for the treatment of DNA mismatch repair-deficient cancers. Cancer Res 71 1836-1848... 

Friedman HS, McLendon RE, Kerby T, et al. DNA mismatch repair and 06-alkylguanine-DNA alkyltransferase analysis and response to Temodal in newly diagnosed malignant glioma. J Clin Oncol 1998 16 3851-3857. 

There are two major forms of hereditary susceptibility to colon cancer.00 Familial adenomatous polyposis is caused by defects in the APC gene (see Chapter 32). The more common hereditary nonpolyposis colorectal cancer (HNPCC), which includes many endometrial, stomach, and urinary tract tumors, results from defects in DNA mismatch repair. -)) The proteins hMSH2 and hMSLl are homologs of the E.coli MutS and MutL (main text). 

Francia G, Green SK, Bocci G, et al. Down-regulation of DNA mismatch repair proteins in human and murine tumor spheroids implications for multicellular resistance to alkylating agents. Mol Cancer Ther. 2005 4 1484-1494. 

Figure 23.12. Bidirectional mismatch repair in E. coli. MutS binds to mismatches formed by errors made during replication. MutL binds to the MutS-bound complex. MutH incises the newly synthesized strand next to the unmethylated GATC sequence. The green arrows indicate signally between the two sites of activity. DNA helicase II unwinds the DNA and exonucleases excise the DNA from the point of incision up to and including the incorrect base. DNA Pol III synthesizes new DNA to replace the excised DNA. (Reproduced with permission from Iyer, R. R., Pluciennik, A., Burdett, V., and Modrich, P. L. DNA mismatch repair Functions and mechanism. Chem. Rev. 106, 302-323, 2006.)...

MSH2 Human non-polyposis colon cancer DNA mismatch repair Colon, uterus... 

Kunkel TA, Erie DA. DNA mismatch repair. Annu. Rev. Biochem. 2005 74 681-710. 

Schofield MJ, Hsieh P. DNA mismatch repair molecular mechanisms and biological function. Annu. Rev. Microbiol. 2003 57 579-608. 

Iyer RR, Pluciennik A, Burdett V, Modrich PL. DNA mismatch repair functions and mechanisms. Chem Rev. 1996 106(2) 302-323. 

Figure 27.51. Mismatch Repair. DNA mismatch repair in E. coli is initiated by the interplay of MutS, MutL, and MutH proteins. A G-T mismatch is recognized by MutS. MutH cleaves the backbone in the vicinity of the mismatch. A segment of the DNA strand containing the erroneous T is removed by exonuclease I and synthesized anew by DNA polymerase III. [After R. F. Service. Science 263(1994) 1559.]...

Bronner CE, Baker SM, Morrison PT, Warren G, Smith LG, Lescoe MK, Kane M, et al. Mutation in the DNA mismatch repair gene homologue hMLHl is associated with hereditary non-polyposis colon cancer. Nature 1994 368 258-61. 

Peltomaki P. Deficient DNA mismatch repair a common etiologic factor for colon cancer. Hum Molec Genet 2001 10 735-40. 

Strand M, ProUa TA, Liskay RM, Petes TD. Destabilization of tracts of simple repetitive DNA in yeast by mutations affecting DNA mismatch repair. Nature 1993 365 274-6. Erratum in Nature 1994 368 569. 

R704 P. Polaczek, DNA Mismatch Repair (MMR) Evolution of the System from Bacteria to Humans , Kosmos (Krakow), 1999, 48, 353... 

Several human DNA mismatch repair genes are associated with hereditary nonpolyposis colon cancer (HNPCC). One of these mismatch repair genes (hMSH2) is located on the short arm of chromosome 2 others are located on chromosome 3. Defects in any of these DNA repair genes predispose individuals to colon cancer as well as to other cancers. 

MSHl, MLH2, DNA mismatch repair hereditary non-polyposis... 

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