Recombinant Human MLH1 protein (GST tag N-Terminus)

Specifications

Form

Liquid

General info

Function

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-MSH3) 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.

Sequence similarities

Belongs to the DNA mismatch repair MutL/HexB family.

Post-translational modifications

Acetylated (PubMed:30770470). Deacetylated by HDAC6 which prevents the MutL alpha complex, formed by the MLH1-PMS2 heterodimer, from being recruited to the MutS alpha complex, formed by the MSH2-MSH6 heterodimer, leading to tolerance of DNA damage (PubMed:30770470).. Ubiquitinated by UBR4; leading to proteasomal degradation. This ubiquitination is counteracted by the deubiquitinase USP5.