Mismatchreparasjon

Mismatch repair is a highly conserved biological pathway that functions to maintain genomic integrity by repairing mismatched bases that escape proofreading during DNA replication. This process is crucial for preventing mutations and ensuring the fidelity of genetic information.

The mismatch repair system is particularly well-studied in bacteria, such as Escherichia coli, and in eukaryotes, including humans. In bacteria, the system involves proteins like MutS, MutL, and MutH, which work together to recognize and excise mismatched bases. MutS identifies the mismatch, MutL interacts with MutS to form a complex, and MutH introduces a cut in the DNA strand containing the error, allowing the excision and resynthesis of the correct sequence.

In eukaryotes, the mismatch repair process is more complex and involves homologs of the bacterial proteins, such as MSH2, MSH6, MLH1, and PMS2. These proteins form complexes that recognize and repair mismatches, with MSH2 and MSH6 forming a heterodimer to identify the error, and MLH1 and PMS2 forming another complex to facilitate the excision and resynthesis of the correct DNA sequence.

Deficiencies in the mismatch repair system are associated with increased mutation rates and a higher predisposition to certain types of cancer, such as colorectal cancer. In humans, hereditary non-polyposis colorectal cancer (HNPCC), also known as Lynch syndrome, is often linked to mutations in the mismatch repair genes MLH1, MSH2, MSH6, and PMS2.

Overall, mismatch repair is a vital mechanism for maintaining genomic stability and preventing the accumulation of mutations that can lead to disease.