Zeta MLH-1 Antibody. Zeta’s mouse monoclonal antibody recognizes MLH-1, a gene where defects cause hereditary non-polyposis colorectal cancer type 2 (HNPCC2). MLH-1 is a protein of 83kDa that heterodimerizes with PMS2 to form MutL alpha, a component of the post-replicative DNA mismatch repair system (MMR). DNA repair is initiated by MutS alpha (MSH2-MSH6) or MutS beta (MSH2-MSH6) binding to a dsDNA mismatch, then MutL alpha is recruited to the heteroduplex. Assembly of the MutL-MutS-heteroduplex ternary complex in presence of RFC and PCNA is sufficient to activate endonuclease activity of PMS2, which introduces single-strand breaks near the mismatch and thus generates new entry points for the exonuclease EXO1 to degrade the strand containing the mismatch. DNA methylation would prevent cleavage and therefore assure that only the newly mutated DNA strand is going to be corrected. MutL alpha (MLH1-PMS2) interacts physically with the clamp loader subunits of DNA polymerase III, suggesting that it may play a role to recruit the DNA polymerase III to the site of the MMR. MLH-1 is implicated in DNA damage signaling, a process, which induces cell cycle arrest and can lead to apoptosis in case of major DNA damages, and MLH-1 heterodimerizes with MLH3 to form MutL gamma, which plays a role in meiosis.
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