MLH1
MLH1 (mutL homolog 1, also known as HNPCC, FCC2, HNPCC2, MLH-1 and COCA2) is a nuclear DNA mismatch repair protein. It heterodimerises with PMS2 to form MutL alpha and with MLH3 to form MutL gamma. Browse Assay Genie's current range of MLH1 research reagents below, or read on for the biology behind the target.
MLH1 is a core component of the post-replicative DNA mismatch repair (MMR) system. It heterodimerises with PMS2 to form MutL alpha. Repair begins when MutS alpha (MSH2-MSH6) or MutS beta (MSH2-MSH3) binds a mismatch in double-stranded DNA, and MutL alpha is then recruited to the heteroduplex. Assembly of the MutL-MutS-heteroduplex ternary complex, in the presence of RFC and PCNA, is sufficient to activate the endonuclease activity of PMS2. PMS2 introduces single-strand breaks near the mismatch, creating new entry points for the exonuclease EXO1 to degrade the strand that carries the error. DNA methylation prevents cleavage, so only the newly synthesised strand is corrected.
MutL alpha (MLH1-PMS2) also interacts physically with the clamp loader subunits of DNA polymerase III, which suggests a role in recruiting the polymerase to the site of repair. Beyond repair, the MLH1 protein is implicated in DNA damage signalling, a process that induces cell cycle arrest and can lead to apoptosis after major DNA damage. When it heterodimerises with MLH3, it forms MutL gamma, which has a role in meiosis. The MLH1 gene belongs to the MutL/HexB family and sits in the HGNC groups MutL homologs and the BRCA1-associated genome surveillance complex.
The gene was identified as a locus frequently mutated in hereditary nonpolyposis colon cancer (HNPCC), which accounts for the HNPCC and HNPCC2 aliases. The HGNC previous names, mutL (E. coli) homolog 1 (colon cancer, nonpolyposis type 2), reflect this link and the bacterial MutL origin of the family. Mouse and rat both carry an Mlh1 ortholog, so the protein is studied across common model systems.
MLH1 forms MutL alpha with PMS2, which activates PMS2 endonuclease activity and directs removal of the mismatched strand with EXO1.
The MLH1 gene is frequently mutated in hereditary nonpolyposis colon cancer, making it central to studies of inherited cancer predisposition.
MLH1 is implicated in DNA damage signalling that induces cell cycle arrest and can lead to apoptosis after major damage.
Heterodimerisation of MLH1 with MLH3 forms MutL gamma, which plays a role in meiosis.
MLH1 partners with PMS2 to form MutL alpha, which is recruited to mismatches recognised by MutS alpha or MutS beta. Activated PMS2 nicks the DNA near the mismatch, allowing EXO1 to remove the faulty strand. MLH1 also contributes to DNA damage signalling.
MLH1 stands for mutL homolog 1. Aliases and earlier symbols include HNPCC, FCC2, HNPCC2, MLH-1 and COCA2. The UniProt recommended name is DNA mismatch repair protein Mlh1. Earlier HGNC names referred to colon cancer, nonpolyposis type 2.
Mouse and rat both have an Mlh1 ortholog. The human gene was identified as a locus frequently mutated in hereditary nonpolyposis colon cancer. Check the datasheet of any product for its validated reactivity.
Other mismatch repair proteins, MutS and MutL partners and DNA replication factors that act with MLH1.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P40692; product specifications from Assay Genie datasheets.