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MLH1

mutL homolog 1

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. It 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. Also implicated in DNA damage signaling, a process which induces cell cycle arrest and can lead to apoptosis in case of major DNA damages. Heterodimerizes with MLH3 to form MutL gamma which plays a role in meiosis.

Gene Name: mutL homolog 1
Synonyms: MLH1, COCA2, FCC2, HMLH1, HNPCC, HNPCC2, MutL protein homolog 1
Target Sequences: NM_000249 NP_000240.1 P40692

Publications (1)

1
An interstitial deletion at 3p21.3 results in the genetic fusion of MLH1 and ITGA9 in a Lynch syndrome family. Meyer C, Brieger A, Plotz G, Weber N, Passmann S, Dingermann T, Zeuzem S, Trojan J, Marschalek R. Clinical cancer research : an official journal of the American Association for Cancer Research. 2009 15:762-9. (WB; Human) [PubMed:19188145]

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The data on this page has been compiled from LifeSpan internal sources, the National Center for Biotechnology Information (NCBI), and The Universal Protein Resource (UniProt).