In eukaryotes is associated with the DNA replication temporarily mismatch repair (MMR), it is not clear how strand-specific MMR Whether is directed. We fused the Saccharomyces cerevisiae MSH6 and cyclin to limit the presence of the G2 / M phase of the cell cycle or S phase or MSH2, MSH6 mismatch recognition complex. While there is a defect in MSH6-G2 / M cyclin synthesis cyclin synthesis of MSH6-S, is an attempt to suppress the variation of the three loci replicated in mid-S phase. However, the functional MMR, MSH6-G2 / M cyclin fusion is a slow printing area very genome. In contrast to the hetero functionality of the recombinant MMR rejection at the time it is partially functional during both the G2 / M phase and S phase. These results connection MMR temporary indicates the rejection of the hetero DNA replication.

MMR mechanism, has been the subject of much discussion. It is not on the experimental results of the controversy surrounding the trans mechanism cis and save MMR system and many bacteria. There is a consensus biochemical properties of protein MMR considerably. Instead, the discussion will focus on the interpretation, I explained the mechanism of MMR biologically relevant experimental results. The cis initial model, they evidence the spiral does not appear but, MMR proteins are said to be able to form a nucleoprotein filament mismatch DNA to the start site. For the other models, was affected by the fact that ATP and mispairs distinction as (MutS MSHS, of homology) homologue of eukaryotic and CIS MMR Hano MutS. Mispair the MSHS and MutS challenge bound in ATP is able to capture containing DNA from end blocks of DNA indicates that occur in the dissociation DNA helix by pairing erroneous. This score is interpreted as aggressive move on the similarity of previous type I and III of the restriction enzyme.

MutS, however, the hydrolysis of ATP to give ADP-bound form that MutSβ is bound to subjected to hydrolysis of ATP-driven translocation (MSH2-MSH3 hetero eukaryotic) and (MSH2, MSH6 hetero eukaryotic) MutSα that it is not degraded mismatch is apparent. Instead after causing structural changes slidably in DNA, bound in the bound MutS mismatch hydrolysis ATP,. ATP was predicted to act as a cofactor to induce a conformational change of the specific Thus, to obtain such a structure pinch on the basis of a comparison of the structure of the ATP-ase RAD50 and MutS structure of ADP bound. This mechanism is possible to load the MutS dimer some dimer thereof, for example, DNA is through four interface to produce a DNA sequence such as that these observations may be interacting Te (MutS the required initial stages of ATP hydrolysis, hydrolysis-driven rotation) does not occur. The tetramer MutS and of, but not be able to mediate the DNA helix of communication, without the need especially for MMR, the structure of this type, report of four for MSH of complex eukaryotes.

Emphasize that it is the subject of MutS / Mutl with Mutl association with a long residence time in mispairs in MutS of ATP-challenging complex ATP load state of MutS of unlike models of MMR transformer. The mismatch, come from the analysis of the activation disgruntled there was a reaction in which the substrate has been hemi GATC, the first evidence of the transformer model, second most effective if both sites are the same criteria . It can be interpreted as a failure of the reaction absent Mutl assembly models only sliding transformer of MutS. The ease with MutS relative sliding can be also not a substrate access to naked DNA, blocking, there is a potential problem. Complex eukaryotic or their equivalents MutS Mutl / a, despite the fact that this is resistant to sliding. , Also, MutSαMSH2 complex of MMR-deficient mutant dominant – it retains the ability to assemble (MLH1, PMS1 Saccharomyces cerevisiae) the MutLα, and emphasizes the importance of the sliding But MSH6-G1142D failure sliding.

I tested an important aspect that distinguishes the model of trans and cis direct Modri ​​ch and Pluciennik: requirement of the DNA helix and block continuous. In one experiment, they show that the binding of EcoRI to reduce the inactive mutant catalytically into the EcoRI recognition site located between the hemi GATC site mating erroneous, but depends mismatches Muth activation does not eliminate. It is suppressed due to the fact that it is not possible binding proteins firmly take 100% and attachment time of the place even in complete absence of the reaction. In the second experiment, and is used for double strand breaks to eliminate completely Muth activated and ends at a short distance between the hemi GATC plasmid mismatched. The results of a simple experiment these elegant, fall at a right angle to the cis-activation mechanism Chelsea side.

Each system that is widely used two using a URA3 gene LACZ bacteria or yeast either gene fusion and slip or recovered URA3 function – can be identified by selecting the loss galactosidase. At the end of the base, the LYS2  Systems have been developed to monitor the mono track stability  composition and different sizes. Type of system latter increased 3-4 orders of magnitude when it is completely inactivated yeast MMR system is particularly useful for detecting subtle mutator phenotype by mutations long mononucleotide. While involved in the repair of various subsets of mutant intermediates MSH6 and MSH3, genetic evidence suggests that it is necessary for MSH2, each mismatch correction in nuclear DNA within. MSH6 mutant CYC1 base substitution analysis showed no detectable increase in the mutation rate, and MSH2 is, have a mutator phenotype of the same mutant MSH3.

These data have demonstrated that MSH2-MSH6 complex intermediate base substitution only, and are involved in the removal of in transformation experiments with double-stranded DNA mismatch-containing heteroaryl, MSH2-MSH3 complex base based on Mismatch repair sequence and context strains showed that it may have a role in most cases. It Depending mismatch base and a minor role in recognition of MSH3, to suppress recombination divergence between the sequences consisting only of the base substitution mutation is important. Conversion rate of alleles that can be returned in the same intermediate is very large, important outcome of the meeting of the CYC1 study was the difference in MMR-related. For example, the TA TA transversion GC GC and can be included or G / C to / T mismatch as mutation intermediates, but the former type of mutation, become 1,000 times than the latter more often. (E.g., 8 – GO or oxoguanine) bases undergo oxidative damage of DNA template MMR system, is important if for removing the base of the normal which is inserted against that can explain the reversal rate variability There it was suggested. OGG1 and MSH6 gene () MSH2, and lesion GO, MSH2 (b) / to go from particular DNA product work after that – to demonstrate the synergistic interaction of removal between genes indicating the high affinity of MSH6, this prediction mispairs, it has not been confirmed.

There is very low in general, MSH6 or MSH3 variant analysis are unique within  MSH3 MSH6 double mutant and mutator phenotype, shows a mutator phenotype very strong equivalent mutations and MSH2. MSH2 – MSH2-MSH3 complex and MSH6 Experiments competition for repairing the intermediate of the frame containing the extrahelical loop of 2 NT or 1, a simple amount of from 20 BP 1 base pair – who are MSH2 only is changed repeatedly is, I have a repair activity for expanding the chain show-MSH3 complex. In this study, it is shown that NT extrahelical loops greater than about 15 did not receive MMR, but suggests that it is possible lines of about 100 points are removed by the MSH2-MSH3 using the system another analysis are. The slight differences mutation data can be determined, the sequence context mismatch recognition, and assuming that it is an important element of the reconstruction process and / or obtained using a variety of assays.

The results obtained in the analysis plan homopolymer of in vivo and in vitro mismatch binding assay, it was shown that it is possible to sequence context has a large impact on the efficiency of MMR. When comparing themsh2 spectrum of the spectrum obtained by the wild-type strain, frame mutation shows a proportional increase larger than the base exchange in both analyzing of SUP4-O forward mutation and CAN1. As E. coli, yeast MMR system shows than performing base substitution of the intermediate efficiently correcting the intermediate frame, and that. Further, experiments frame specific example, MMR system as yeast, such as EE system eliminates the mutant intermediate sequence analyzed by suggesting effectively confirmed as compared to the non-repetitive sequences. Unlike E. coli, the MMR system time, display a strong preference for the repair of transition beyond the base substitution of transversion intermediates, the SUP4-O system experiments, MMR system of yeast, repair transversion intermediate to show to the very low tolerance has been shown.

Both of MutS function of complex yeast and Mutl component  Correct mutation middle. The study, mutation rate, phenotype ofmlh1,
Most of the mismatch PMS1, andmsh2mutants suggested distinction is usually stick that are in need of hetero complex of PMS1 MSH2-MSH6 complex and Mutl protein MLH1 repair the MSH2-MSH3,. (MLH3 and MLH2) Minor additional activity Mutl cognate two, however, have been identified, they are supposed to act as a heterodimer complex with MLH1 to correct the distortion that is recognized by the MSH2-MSH3 complex . Interestingly, PMS1 mRNA only be yeast cell cycle regulation, complexes comprising MLH1, different, increase the likelihood that exist in different times during the cell cycle. Therefore it is possible to dominate the synthesis of DNA, other complexes might be important for DNA repair disorders arising from the context of the DNA replication of normal, MLH1/PMS1 complex, most of the replication error I corresponds to.

May be due to the recombination induce or modify spontaneous or replication errors, the base is mispaired and unpaired base in DNA. Major route of elimination of contradiction that occur during replication is MutHLS time of E. coli and related pathways of other organisms. By an incision to repair MutS hemi methyl dam site, it begins by binding to activate the mismatch of an intermediary Mutl endonuclease Azimut the direction discrimination. Mutl homologous to MutS more than one is present in eukaryotes that plays a variety of roles in the recombination or mismatch repair (MMR) pathway. Suggesting that the direction determination is different E. coli homologue not Muth has not been identified in eukaryotes. Repair MSH2 hetero – can be initiated by the MSH2-MSH3 (MutSbeta) and MSH6 (MutSalpha). It seems to be interesting, you lack a present such as fission yeast or genome, such as MSH3 Drosophila some, but to play the role of MMR. MLH1-PMS1 (MutLalpha) is homologous hetero main Mutl. Once again, rather than a part, all eukaryotes to form a heterodimer with MLH1, you have the Mutl homologues of additional plays a minor role of MMR. Function is ε and DNA polymerase delta and, EXO1 PCNA perhaps additional factors, in the MMR of eukaryotes. Discrepancies and some factors that can be processed or MMR-independent pathway is a flap endonuclease FEN-1 and (BER) glycosylase DNA nucleotide excision repair (NER), base excision repair part. Established in how to modify the line about 16 to several hundred of unpaired nucleotides and Saccharomyces cerevisiae once. Chain such a large scale can not be processed by the MMR.

associated to arise the antirecombination replication errors mutation avoid removing the mutation potential to prevent not identical (homeologous), DNA recombination between sequences: mismatch repair DNA in E. coli, participate in the process of two separate that you have been shown. You are familiar with for multiple copies of the plasmid to avoid mutation, we shows you (which removes the 53 amino acid C-terminus of MutS of) the cell mutation mutSDelta800. In genetic crosses between species, however, the recipient is to increase the recombination of MutS 280-fold relative in mutSDelta800 mutation show +. Are resistant to cisplatin mutSDelta800 mutation protein, but not the dam bacteria explanation, why it binds the MutSDelta800 O6-methylguanine gap in the chain platinated GG cross-link to because you do not MNNG toxicity. This indicates that less important for the C-terminus of MutS resulting, to avoid mutations are required for cisplatin and sensitization antirecombination. The inability to form a MutSDelta800 tetramer, it can be shown that they are in the form of MutS active.

associated to arise the antirecombination replication errors mutation avoid removing the mutation potential to prevent not identical (homeologous), DNA recombination between sequences: mismatch repair DNA in E. coli, participate in the process of two separate that you have been shown. We have shown (to remove the 53 amino acid C-terminus of MutS of) that are familiar to multiple copies of the plasmid to avoid mutation, the cell mutation mutSΔ800. In genetic crosses between species, however, recipient with the 800 mutation show increased recombination of MutS to 280-fold relative +. Instead of the O6-methylguanine mismatch and join in the chain, why are resistant to cisplatin platinated dam bacteria mutSΔ800 mutation description, but the GG cross-linking, MutSΔ800 protein, will not MNNG toxicity. This indicates that less important for the C-terminus of MutS resulting, to avoid mutations are required for cisplatin and sensitization antirecombination. Inability 800 to form a tetramer, it is possible to indicate that they are in the form of MutS active.