mismatchrepairilla

Mismatch repair (MMR) is a crucial DNA repair system found in all known organisms. Its primary function is to correct errors that arise during DNA replication, such as base-base mismatches and small insertions or deletions. These errors can lead to mutations if left uncorrected, potentially causing cellular dysfunction and diseases like cancer.

The MMR system operates by identifying and removing mismatched nucleotides from newly synthesized DNA strands. It achieves this by distinguishing between the parent DNA strand, which is generally considered correct, and the newly synthesized strand, which may contain errors. This distinction is often based on transient chemical differences, such as methylation patterns, that exist immediately after replication. Once an error is detected, MMR proteins are recruited to the site. These proteins excise a segment of the newly synthesized strand containing the mismatch and then DNA polymerase fills the gap, followed by DNA ligase sealing the nick.

In eukaryotes, the key components of the MMR system include proteins like MutS homologues (MSH2, MSH6, MSH3) and MutL homologues (MLH1, PMS2). In bacteria, the system is primarily composed of MutS and MutL proteins. Defects in MMR genes are strongly associated with a high mutation rate and genomic instability, contributing to the development of various cancers, including Lynch syndrome, a hereditary form of colorectal cancer. Therefore, MMR plays a vital role in maintaining the integrity of the genome.