Originally, the protein is specific to the system that has been identified in prokaryotes MMR when the loss has improved the accumulation of results in mutator phenotype errors and DNA replication. The first step in troubleshooting replication errors by MMR system, includes eficient recognition spiral failure due to sliding of the DNA polymerase mistake or nucleotide incorporation of (gap). Then, DNA strands newly synthesized containing erroneous information is that it is selectively removed, are synthesized again. Is an essential feature of the MMR system of all, lack of replication error seems to only be used as a template for repair strand discrimination as necessary to repair it. Whereas requires a protein involved in the process of common DNA metabolism, procedures and removal mismatch recognition initial final stage of MMR may require special Mut proteins are evolutionarily conserved highly to. Hereinafter, mechanism of the prototype system MMR and E. coli proteins are described in the relevant MMR components that are identified from a variety of eukaryotic organisms.
Mismatch repair (MMR) system is critical to maintaining the overall Integrity of the genetic material, and the main features of this system. It is stored in the course of a highly evolved. MMR system is well-known for his role best. Located on the lower level acceptable repair after replication of DNA polymerization errors is important in order to maintain the mutation. In addition to the recognition replicationgenerated mismatch, also MMR proteins, but it is only intended to correct the mismatch in the hetero.
Recombination intermediates. Mismatch recognition in recombinant intermediates can induce the repair process leading to genetic transformation the gene is found Can cause anti-recombinant activity to prevent recombination events to go to completion or event,. Anti-recombination activity of MMR. Protein promotes genomic stability by suppressing the reaction between the divergent Sequences from different organisms, or present in the genome of a single. In addition to recognition and processing of DNA mismatch, including Äúnormal, the AU, The base MMR system, I play a role in response to DNA damage. In the end, MMR eukaryotic proteins have, recombination of roles not related to non-compliance Protein and some identification, have evolved an important role in the metabolism meiotic chromosome. This assessment summarizes the different roles of MMR proteins. To promote genetic stability, we are focused on the impact of MMR of genetic defect.
The (MMR), 2 (PMS2) protein that is also known as PMS1 protein homolog 2, separation meiosis after increased the DNA mismatch repair. Members of PMS2 gene family has been found in a cluster of seven on chromosome. Protein of PMS2 96 kDa is PMS1, and MLH1, MLH3 mismatch repair closely related is the homolog of gene Mutl of bacteria. Coordinate bond This complex of other proteins, PMS2 protein heterodimers with proteins MLH1 that are activated in the presence of ATP to repair errors that occurred during cell preparation of DNA for cell division I will form a.
Loss of PMS2 expression in tumors, can determine the suitability for mutation analysis is useful in identifying a mutation carrier hMLH1. The defect account of PMS2 gene for a significant proportion of tumor microsatellite instability and, for a significant percentage of small but colon cancer. Dominant genetic disorder associated with changes in the HNPCC syndrome known as Turcot syndrome, hereditary colon cancer, nonpolyposis (HNPCC) is clearly too much, PMS2 is associated with.
Nonpolyposis, also known as Lynch syndrome (HNPCC) is an autosomal that the colon, uterus, stomach, as well as upper urinary tract, and predispose individuals to the development of other cancers also, colon cancer is hereditary is a dominantly inherited cancer syndrome. People with HNPCC / Lynch syndrome, have a germline mutation in one of several genes involved in DNA mismatch repair. Most of the mutations that are associated with the occurrence HNPCC / Lynch syndrome in the MLH1 and MSH2, but mutation of PMS2 and MSH6 have also been identified.
There are family history and / or personal, some strategies for individuals to evaluate a measure of HNPCC / Lynch syndrome cancer. Typically, the first step, the HNPCC / Lynch syndrome involving loss of protein expression of one or more and (the presence of a set of types changes repetitive DNA called microsatellites) Microsatellite instability genes associated with HNPCC / Lynch syndrome is to evaluate tumor characteristics common to people with.
Immunohistochemistry microsatellite instability and (MSI) (IHC), is interpreted together in order to assess the risk of HNPCC / Lynch syndrome generally. This suggests a defect DNA mismatch repair high level of MSI in the tumor, but this knowledge does not provide a gene information involved. Used to evaluate the protein PMS2 in HNPCC / Lynch expression of MLH1, and MSH2, MSH6,, test strategy, IHC is a cancer-related syndrome further. Loss of expression of one or more of these proteins in tumors, it will be useful to identify that it should be analyzed genes associated with mutations of interest (s). IHC and MSI are read together, but they also, separately in order to respond to the clinical situation in which barriers to be run these tests at the same time (for example, financial problems, requirements of the sample) and is present are available.
You can determine the loss or retention of PMS2 protein expression and MLH1, MSH2, MSH6 in IHC alone. When the protein all four are present as approximately 5% of the tumors that display MSI with normal expression of the four proteins these genes, potential HNPCC / Lynch syndrome is reduced but not eliminated. Loss of protein in one or more of IHC shows the probability of HNPCC / Lynch syndrome is increased and DNA mismatch repair of incomplete tumor. Germ cell test Each gene (s) (i.e., mutation analysis) it is possible for to identify germline mutations cause, is performed in order to enable testing of individuals predicted risk.