Mismatch DNA Repair (MMR)

Overview of DNA Mismatch Repair (MMR)

DNA mismatch repair (MMR), a conserved process for detecting and correcting errors made during DNA synthesis, is crucial to the maintenance of genomic integrity. In prokaryotes, a MutS homodimer recruits a MutL homodimer to sites of DNA mismatches. In eukaryotes, six MutS homologues (MSH1-6) and four MutL homologues (MLH1, PMS2, PMS1, and MLH3) have been identified. Heterodimers composed of two MutL homologues detect distinct DNA mismatch lesions, and heterodimers composed of two MutS homologues perform the repair. Other factors required for MMR in eukaryotes are EXO1, PCNA, RFC, RPA, DNA polymerases, and DNA ligases.

MMR Deficiency and Microsatellite Instability (MSI)

Microsatellite instability (MSI) is a predisposition to genetic mutation resulting from MMR deficiency (dMMR). High MSI (MSI-H) arising from dMMR results in Lynch syndrome, also known as hereditary non-polyposis colorectal cancer (HNPCC). Lynch syndrome is associated with colon cancer, as well as other human cancers. MSI and dMMR are strongly associated with tumor responsiveness to immune checkpoint blockade. MSI status can be determined through PCR amplification of microsatellite markers and/or immunohistochemical detection of MMR proteins MLH1, PMS2, MSH2, and MSH6. The absence of expression of any of these MMR proteins indicates dMMR.

Illustration of eukaryotic MMR system. 

Relevant Antibodies

Flora Flora is a technical support expert at EnkiLife, familiar with immunology and neuroscience, dedicated to providing customers with high-quality product combinations and technical support to help achieve research in neurodegenerative diseases and other neuroscience areas.