There are al least several notable Mismatch Repair functions . DNA mismatch repair, increase the stability of the genome by correcting the errors that escaped the polymerase correction. One of the most important stages of the DNA mismatch repair identification, a new DNA strand from the parent, such as the need for repair first. In Escherichia coli, endonuclease Azimut potential, has this feature. However, in prokaryotes and eukaryotes most, Azimut all the genes missing. Mutl a protein removal direction mismatch recognition, and determine direction – is an important component of this system to mediate protein-protein interactions.
Therefore, it is believed that the main function of the long Mutl and has adjusted the continuous process mismatch repair. However, recent studies, Mutl homologue most from an organism that has not been saved Muth indicates that associated with the low activity endonuclease, encoding the metal binding motif. To have been found in organisms that rely on DNA mismatch repair you do not disgruntled dependent only Mutl cognate bearing this activity, this finding reveals another important feature of the protein Mutl step in the direction discrimination. In this chapter, in order to explain how to Mutl the endonuclease activity and characterize the multiple functions of Mutl is regulated by the repair of other factors, we will discuss activities and structural features of the recently.
Mismatch repair DNA (MMR) is a pathway that is highly conserved play an important role in the maintenance of genomic stability. Specificity of the MMR is based on the generation insertion / deletion mispairs between the recombinant and DNA replication and base mismatch mainly. It suppresses homeologous recombination Further MMR, plays a role in DNA damage signaling in eukaryotic cells recently have been shown. Homolog of the eukaryotic and Mutl, MutLalpha MutSalpha and is an important player in MMR-related genome maintenance each MutS of Escherichia coli. For example, also are involved in DNA metabolism various routes, such as RPA and PCNA, protein component of many other, is essential for MMR. MMR defects is related to the whole genome instability such as abnormal predisposition and infertility division of mammals and hereditary non-polyposis colon cancer, resistant to chemotherapeutic agents particular, to cancer, some.
The participation of more than one stage of mismatch repair of DNA replication protein of (RPA) to (MMR), however, modulation of the function of the phase between different is unknown. Phosphorylation, we have shown here that you adjust the MMR in RPA function perhaps. In order to facilitate assembly of the starting complex was originally MMR, unphosphorylated RPA is associated with the double-stranded DNA nicks heteroaryl. By gap of single-stranded DNA obtained preferentially in the non-phosphorylated protein to connect, I stimulate the resection probably caused mismatch. Begins to phosphorylate wide resection as a result of reducing the DNA binding affinity of RPA Repeat DNA binding RPA. Therefore, the phase of DNA repair synthesis, easy, RPA was phosphorylated make available DNA template for the re-synthesis by DNA polymerase δ catalyst away from DNA. These observations, to support a model of a method for changing the DNA binding affinity for RPA phosphorylation meet the requirements of the differential stage of the MMR.
As a consequence of exposure to physical agents chemical and exogenous (eg, smoke benzo [a] pyrene, polychlorinated biphenyls, dioxins, and tobacco, DNA damage in cells, asbestos is accumulated over time , UV light, Rn), reactive metabolite, including NOS) and (ROS and nitrogen species endogenous active oxygen. Another source of DNA damage, is an error that occurred during the processing of the DNA of abnormal reaction and metabolism of normal DNA, including DNA replication, repair and recombination. Depending on many factors, including the DNA polymerase specific incorporation of nucleotides miss generates a base mismatches in DNA bases of DNA synthesis by varying the speed. Please refer have a copy of the low accuracy (such as Andersen. While cancer, in general, DNA polymerase, see Kunkel and (McCulloch, the subject of DNA polymerase overcome surrounding the specific sites of DNA damage etc. have a copy of the relatively high replication fidelity), and, in this issue). If it is not removed, DNA damage, has the potential to generate mutations in germ cells and somatic cells can be changed and diseases disorders that cause cell phenotype. To prevent these adverse effects and to protect the integrity of the genome and has several mechanisms to repair damaged DNA, cells prevents mutations thereby. Such a system is a critical path known as DNA mismatch repair.
Thus prevent the mutation, mismatch repair DNA of MMR that occur during DNA replication is permanently dividing cells. MMR defect, increased mutation rate spontaneous MMR, so have reduced the number of errors of replication-related. Hereditary and inactivation of MMR in human cells are associated with human cancers sporadic, MMR system is required for cell death in response to certain types of DNA damage and programmed cell cycle arrest and / or It is a. Therefore, prevention of mutagenesis in tumor formation in both short term and long term damage and cell severely eliminates, MMR plays a role in DNA damage response pathway.