Avoidance in Mammals

Avoidance in Mammals is the simple iteration instability of yeast and E. coli MMR defect  It is important for binding of (MSI or microsatellite instability phenotype) instability characteristic of simple repetition in certain types of cancer in humans because of defects in the MMR.  The most important, mutations in MSH2 and MLH1 is associated with a 60 to 70 percent Cases of hereditary non-polyposis colon cancer (HNPCC), very few HNPCC cases are also associated with mutations in PMS1, in MSH6 and PMS2. But did not have a case without the HNPCC mutations result in MLH3, MLH3 mouse gene map or MSH3 in the seat I sensitivity Colon physical. In a manner analogous to the tumor suppressor gene and a predisposition to HNPCC, individuals heterozygous mutant MMR gene corresponding high increase of the development of subsequent tumor mutations (loss of function expression of a gene) or loss of heterozygosity It is the result of rate.

In addition to HNPCC, MMR defect is associated with sporadic colorectal, endometrial, stomach cancer. Unlike the case of HNPCC, but the majority of cancer sporadic these rather than have identified mutations in MSH2 and MLH1, transcriptional epigenetic silencing is associated with a phenotype of MSI. Specifically, methylation of MLH1 promoter, is associated with a complete loss of protein expression. In addition to the functional inactivation of the MMR system of a mammal by epigenetic mechanisms and genetic protein loss, MMR Defect is due to the overexpression of protein MSH3 Through the joint efforts of Genes MSH3 and adjacent site DHFR. Excess MSH3 full usamotyava MSH2, MSH2 by it – it is possible to prevent the formation of MSH6 complex, to produce a anMSH6mutant equivalent. Finally, it is possible to exert dominantnegative effect was found to HNPCCassociated PMS2 nonsense mutation.

Spontaneous mutation rate, the spectrum of HPRT gene was obtained. Human tumor cell lines MMR defect. Mutations in the forward gene increased several hundred-fold in human tumor cell lines that are deficient in MSH2 and theHPRT MLH1, and increases in proportion, considering a frame from mutation INC1-1 nucleotide substitution. As with MMR-deficient yeast, these sequences, indicates that for the accumulation of protein inactivation, “in jeopardy” and especially that, Monoran is a hot spot frame events in tumor cells Mutation. Indeed, frame shift in mono nucleotides, TGF-pass and APC Both genes are important in colon tumorigenesis have been identified Tumor cells having the phenotype of MSI. HHUA human tumor cell line is deficient in MSH6 and MSH3, the chromosomal transfer experiments, the generation of cell lines is insufficient allowed in only one of the protein.
Study of mutations and microsatellite instability in cell lines of these HPRT Able to repair extrahelical chain size of MSH6 is 1-4 NT is shown, while the I will remove the line MSH3 2-4 NT size. Contrast to the yeast MMR The MSH3/MSH6 functional redundancy system above, it is seen in 1-2 NT for lines, MSH3 is only able to repair the line is greater than 2 HCl. Derivative HHUA, it is assumed to be increasing base substitution mutation MSH3, the failure rate of only surprisingly. In human cells, this means that it may be involved in adjusting the MSH3 intermediate base substitutions. MMR systems in mammals are involved in somatic hypermutation of immunoglobulin genes process variables in response to antigen stimulation, to generate high affinity antibodies. Several studies in other studies, no spectrum, the frequency of hypermutation is changed in MMR-deficient mice is shown, hypermutation full level for MMR It is shown to require a functioning system. Finally, in some studies, involvement of the MMR system has been reported in the course of somatic hypermutation. Recent data shows a serious confusion

As a model of human disease, of MSH2, MSH3, MSH6, knockout mouse This is done or PMS1, PMS2, MLH1,, except all MSH3-deficient animals and PMS1 showed an increased incidence of various Cancer of the internal organs. Provided by genetic studies of yeast, rather than the MMR defect completely, MSH6 mouse is a mouse MSH2 identical with a spectrum of different tumor from knockoutMsh6 MSH3 mouse and double mouse MSH2. Interestingly, there is a possibility that it has a spectrum of different tumors, reflecting the minor role of MLH1-MLH3 and MLH1, PMS1 in mutation avoidance Pms6 mouse and MLH1, both minor differences in mutation rate, show. Mutations either a spectrum MSH6, Each one or PMS2 knockout mice containing Lazi SUPF forward mutation reporter system has been reported. In contrast, PMS2 tissue-specific tumors were observed in mice showed a comparable increase in the mutation frequency is SUPF all tissues examined. The MMR machinery, the popularity of frame mutation in the spectrum of PMS2 mouse is consistent with the general consensus is that it plays a major role in correcting the error of the deviation of the DNA polymerase. The study of lacImutation, as expected with a base substitution, I found a inMsh2mice the mutation frequency was increased mainly. Interestingly the tumor tissue, and comparison