Mismatch repair is a process that is highly conserved in eukaryotes from prokaryotes. Pneumonia obtained from S the first evidence of mismatch repair, (hexane HEXB gene). The cause hypermutable strain following the work of E. coli, were identified inactivated when mutationally, the number of genes. The protein is called “the Mut” gene product, which is the main active component of mismatch repair system. Three of these proteins is essential for the detection of non-compliant, direct the repair mechanism to it. Of MutS, (MutS homologs is Mutl and hexa HEXB) Mutl and Azimut “.
The MutS to form a dimer (MutS2) binds to DNA that recognize mismatched base daughter strand, was mutated. Chelsea will bind hemi-methyl object along the daughter DNA, but Azimut latter and MutS2 and activates the action has not been published, and contact Mutl dimer and (MutL2) bound to the MutS-DNA complex only it functions as an intermediary between the activation. Transfer of DNA, can be in one kilobyte maximum distance in order to find the nearest D of non-compliant (GATC) methylation site. Azimut daughter strand nick UvrD helicase of the two chains of (DNA helicase II) separation near activation of MutS-DNA complexes when, ‘to 5’ 3 dial specific polarity and hemi-methyl site. In order to cut while it passes complex MutSHL across slides along the DNA in the direction of the non-release direction. The deterioration in Ekisopasu SS-DNA complex and tail. 5 ‘or 3’ – adopted exonuclease is dependent on either side of the incision where the mismatch Azimut. It was used in the case is’ (in → 3 ‘exonuclease participants made by Azimut is ExoVII or both RecJ 5), or the end of the mismatch 5’. If the participant is 3, I used the end of the “mismatch, the (enzyme ‘to 5’ 3) ExoI.
In other words, – the whole process, has been completely cut off both the nucleotide and the surrounding site to complete along the gap region. Can be a gap of one strand was created by exonuclease, as a template, by using the other strand, is removed by (assisted by element-binding protein) DNA polymerase III, and sealed by DNA ligase to a final Is the. Damumechiraze is methylated daughter strand shortly thereafter.
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.
Repair of base base mismatch that can occur during DNA replication. Bind to a region of abnormal DNA, proteins, forming starting complex (heterodimer) thereof removed. Loss of MMR proteins accumulation of DNA replication errors in cells growing in the region of the genome in particularly short repetitive nucleotide sequence, a phenomenon known microsatellite instability as (MSI). Thus, in contrast to cell-cell, MMR deficiency of proteins within cells is associated with a high level of MSI (MSI-H) MSI low levels closely (MSI-L), the MSI stable (MSS).
Hereditary non-polyposis colon cancer (HNPCC) it is possible to be mutated in families with children (relative frequency in parentheses), in humans, 9 function MMR gene is identified, they are five: (49%) MLH1 and is a clinical concern specific PMS1 (0.3%), PMS2 (2%), MSH2 (38%), MSH6 (9%). Mutations in more than 300 have been identified. Individuals carrying mutations have MMR of normal proteins, the DNA, including parallel (loss of heterozygosity) nonmutated protein production stops if damaged. The MLH1, and hetero (MMR proteins other mutation has not been found) MLH3 or PMS2, PMS1 if MSH2 forms a complex with hetero and MSH6. If the MSH2 is insufficient, MSH6 protein is lost due to instability of the protein probably.
The repair DNA mismatches needed to maintain the stability of the genome, from prokaryotes to eukaryotes and are well preserved. Insert mismatch base pair deletions, and errors made during replication of DNA, is a substrate for mismatch repair. It is a chain-specific, mismatch repair is for the daughter strand newly synthesized only. To start the mismatch repair in E. coli, introduction of participants Mutl MutS essential, mismatch recognition, and Chelsea target direction, three proteins is mediating the interaction between MutS and Azimut. Mutl important mismatch repair and MutS homolog has been found in almost all organisms. MutS homolog of Mutl and mutations are associated with increased susceptibility to cancer in humans and mouse. In this case, the crystal structure of the nuclease Azimut, save fragments of ATP-ase Mutl (LN40), and make sure the complex of LN40 to another nucleotide. Type II restriction endonucleases and Muth has identified evolutionary relationships between the Muth established based on the crystal structure of the active site. In biochemical studies and crystal recent interaction with MutS and Mutl Single Muth has been shown to regulate by hydrolysis and ATP binding as a molecular switch. The crystal structure of these, I shed light on the general mechanism of the role of mut protein in the prevention of mutagenesis and mismatch repair.