Repair proteins mismatch

Obmolova, G., Ban, C., Hsieh, P. and Yang, W. (2000). Crystal structures of mismatch repair protein MutS and its complex with a substrate DNA. Nature 407, 703-710. 

Mismatch repair protein mutL Single-stranded DNA-binding protein ssb DNA repair uvrA Helicase dnaB RNA polymerase frpoB subunits rpoCJ... 

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. 

A more direct association was made by experiments showing that cis-platin-modified DNA is recognized by mismatch repair proteins. The Mut-S a heterodimer, a putative mismatch recognition factor, binds to a 32-bp... 

Fig. 4. Possible role of mismatch repair in the cytotoxicity of cisplatin. A) During replicative bypass, a mismatch is incorporated across from the cisplatin-DNA adduct. This compound lesion is bound by the mismatch repair proteins, which cut the DNA on the strand opposite the platinum. Repair synthesis would reproduce the same mismatch, resulting in a futile cycle and possibly the accumulation of DNA strand breaks which would activate apoptosis. B) Alternatively, the mismatch repair complex can recognize the cisplatin-DNA adduct alone and generate a signal that triggers apoptosis.

Cellular sensitivity to different platinum compounds and the recognition of the platinum DNA adducts by mismatch repair protein complexes appear to be linked [103]. It may also be significant that hMSH2 is expressed to higher levels in testicular and ovarian tissue than in other organs such as heart, liver and colon [109], Whether or not mismatch repair plays a general role in the anticancer activity of cisplatin still remains debatable, however. Mismatch repair proteins bind to cisplatin-DNA adducts in vitro with weak specificity [109][113]. Although specificity is enhanced when aplat-inum lesion is combined with a mutation [113], it is still less than the affinity of these proteins for the unplatinated mutation [63] [108]. 

McGoldrick JP, Yeh YC, Solomon M, Essigmann JM, Lu AL (1995) Characterization of a mammalian homolog of the Escherichia-coli Muty mismatch repair protein. Mol Cell Biol 15 989-996... 

Culligan KM, Meyer-Gauen G, Lyons-Weiler J, Hays JB (2000) Evolutionary origin, diversification and specialization of eukaryotic MutS homolog mismatch repair proteins. Nucleic Acids Res 28 463-471... 

B.B., Crit. Rev. Immunol. 24, 297-320, 2004 Fiset, P.O., Cameron, L., and Hamid, Q., Local isotype switching to IgE in airway mucosa, J. Allergy Clin. Immunol. 116, 233-236, 2005 Min, I.M. and Seising, E., Antibody class switch recombination roles for switch seqences and mismatch repair proteins, Adv. Immunol. 87, 297-328, 2005 Apian, P.D., Causes of oncogenic chromosomal translocation. Trends Genet. 22, 46-55, 2006. 

Stains for the mismatch repair proteins MLH1, MSH2, MSH6, and PMS2 can be used to screen for MSI-high neoplasms. 

A subset of colorectal cancers arises via the MSI pathway owing to mutations or alterations in specific mismatch repair proteins. This pathway is discussed further later. 

MSI-H/mismatch repair protein-deficient colorectal cancers, evaluated by either MSI testing or IHC, may have a better survival in subsets of colon cancer patients. This effect may be related to the CpG island methylator phenotype (widespread promoter methyla-tion). MSI-H tumors may also respond differently to... 

Medullary carcinomas of the pancreas, like their colorectal counterparts, often show microsatellite instability, which is usually caused by somatic hypermethyl-ation of the MLHl promoter in sporadic cases " and by an inherited mutation in MLHl or MSH2 HNPCC syndrome.Immunolabeling for MLHl and MSH2 reveals loss of expression of one of these DNA mismatch repair proteins in many cases. 

Mismatched base pairs can arise from errors that occur during recombination repair. A variety of prokaryotic and eukaryotic mismatch repair proteins repair mismatched base pairs by a variety of mechanisms that involve the excision of one of the bases [69, 70]. 

The role of NSAIDs in MSI (microsatellite iustability)-high colon cancers has been less clear. MSI-high cancers typically have less expression of putative NSAID targets such as COX-2 and AKT." A number of studies have shown that NSAIDs can induce apoptosis in MSI-high colon cancer cell lines, potentially through induction of pro-apoptotic MMR (mismatch repair) proteins. ... 

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