MutL,MutLα and Heteroduplex Ternary Complex
Increases several times mutations ternary complex hetero Mutl, and MutLα, is a major cause hereditary cancer, nonpolyposis colorectal cancer (HNPCC). Fidelity of genetic recombination biosynthesis of DNA, and genetic stability provided by this system, correcting its role in ensuring his participation in the apoptotic response checkpoint and several classes of DNA damage I’m due to its role in. Responsible for the reaction is best understood in molecular terms replication of error correction.
Mismatch repair mechanism is most detailed in E. coli, E. coli reaction was dissolved in purified systems. Repair is focused on transient absence daughter strand of the replication fork (GATC) methylation d in DNA newly synthesized. It is initiated by the binding of MutS to Mutl mismatch and have adopted the ATP-dependent DNA repair after hetero of the MutS. Ternary complex of hetero MutS • • is sufficient to activate D of Azimut incision of unmethylated strand (GATC) endonuclease activity assembly Mutl. Instruct the repair new DNA strands, acts as an entry point of the cutting system, disconnection of the subsequent circuit is the actual signal consisting DNA helicase II, with an appropriate single-stranded nuclease. The pairing 5 ‘to 3’ hydrolytic activity mis-3 ‘-to-5:00 thread suspended Azimut 5’, there is a need, but the mismatch. Ligase, to restore the integrity of shared spiral gap, and ‘is required when Muttonikku is 3 introduced exonuclease’ repair of the DNA polymerase III holoenzim then.
Mammalian cell extract supports such reactions is indicated by (gap or nickname) strand breaks can be repaired but to reside the non-compliance ‘or 5’ 3. Major protein for the initiation of mismatch repair of eukaryotic organisms, is a cognate Mutl and MutS of bacteria. Port 2 mismatch recognition activity of eukaryotic, MutSα and (MSH2 • MSH6 hetero) MutSβ (MSH2 • MSH3 hetero), MutSα but is the responsibility of the event mismatch repair in most mammalian cells probably. Homologue of eukaryotic Mutl functions as a hetero MLH1 can function as a common subunit. The best (MLH1 • PMS2 heterodimer), is separated from both yeast and human (a MLH1 • PMS1 complex), these features are MutLα.
DNA binding protein replication clamp PCNA, RFC-clamp loader, single-stranded DNA binding protein RPA, exonuclease I, and DNA polymerase δ: the study of mammalian reaction extract, in addition to MutLαMutSα and MutSβ in mismatch repair for the participants, HMGB1 it was involved, the activities of six. Surprisingly, as the 3 ‘, in the absence of other proteins necessary for 3′-led and repair of 5′-GG or GT mismatch in the extraction of cells of human and mouse to 5’-polarity ExoI hydrolysis of double-stranded DNA,. However, it is much less than the increase to 150 times by MSH2 deficiency HPRT volatility of these cells, extract from the line of mouse ExoI cells, insertion / deletion of a single base dinucleotide and important activities had increased 30-fold and I was holding the hetero. Spectrum of HPRT mutations have not been established, such as Wei. The study not only suggests that it plays an important role in MutSα-dependent repair of base mispairs underlying ExoI, the cutting operation an alternative, these data can be made to function insertion / deletion mismatch correction I could.
The observations of these results led to the system some friendly that support participants, and ordered the excision repair and causes mismatch. MutSα, MutLα, ExoI, simple and most of them are composed of RPA. Hydrolysis is a mismatch cause in this system, but to manage the resection always, you can run the 5 ‘to 3’ from the participants. It is not a MutLα required for this system, but it mismatch dependence of the hydrolysis reaction does not improve by suppressing the mismatch of ExoI without DNA.
System that MutSα, MutLα, ExoI, and to support the removal of two-way to complement the RPA in RFC and PCNA, resection to receive that is, place the non-compliance or 5 ‘or 3’ led by the participants. Unlike the simple 5 ‘to 3’ reaction, 3 ‘led resection is dependent PCNA MutLα completely, and RFC. RFC plays two roles in the activation of clear 3 ‘oriented resection. It acts directly to ‘not required for activation of oriented excision, mismatch ExoI mediated 5′ 3 to suppress the hydrolysis’ according to gap or to 3 ‘3 position nickname function as a load PCNA loader in the form of PCNA You. The activity of ExoI other than those used in this study, the 3 ‘-oriented resection of this system for ExoI, ExoI active site mutant was therefore does not support the hydrolysis intact and without exonuclease activity. The addition of DNA polymerase δ in six components these is a system that supports the mismatch repair reaction can be oriented in the direction of the rest which is located in the non-compliant ‘or 5′ 3. As well as the 5’-oriented resection, without independent MutLα necessary to repair synthesis steps of 5 ‘-oriented repair reaction in this system, it is RFC and PCNA.
The tasks described here, shows the function of ExoI and MutLα in mismatch repair of human. MutLα indicates that there is a potential endonuclease that is activated ATP-dependent mismatch, MutSα-, RFC-, and PCNA-we. Hetero cutting this 4 protein system is broken towards the direction of refraction is biased strongly. Mismatch, including the span segment was cut from the action “of the 5 ‘to 3 of MutSα activity ExoI then by a two-strand breaks.