MSH3

Overview

Crystal structure of the MutSb complex of MSH2-MSH3.

MSH3 is a gene that encodes a protein involved in the DNA mismatch repair (MMR) system. This system is crucial for maintaining genomic stability by correcting errors that occur during DNA replication. MSH3 forms a heterodimer with MSH2, another protein in the MMR pathway, to recognize and initiate repair of insertion-deletion loops and other mismatches in the DNA.

Function

The MSH3 protein, in conjunction with MSH2, forms the MutSb complex. This complex is specifically involved in the repair of insertion-deletion loops, which are common errors that occur during DNA replication and recombination. The MutSb complex recognizes these errors and recruits other proteins to excise the incorrect DNA segment and resynthesize the correct sequence.

Structure

Detailed view of the MSH2-MSH3 interaction.

The structure of the MSH3 protein, as part of the MutSb complex, has been elucidated through X-ray crystallography. The complex is composed of two main domains: the mismatch recognition domain and the ATPase domain. The mismatch recognition domain is responsible for binding to the DNA and identifying errors, while the ATPase domain provides the energy required for the repair process.

Clinical Significance

Mutations in the MSH3 gene can lead to defects in the DNA mismatch repair system, resulting in increased susceptibility to certain types of cancer, particularly colorectal cancer. MSH3 mutations are also associated with hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome.

Related Proteins

MSH3 is part of a family of proteins that includes MSH2, MSH6, and MSH1. These proteins work together in various combinations to recognize and repair different types of DNA mismatches. The MSH2-MSH6 complex, known as MutS_, primarily repairs base-base mismatches and small insertion-deletion loops, while the MSH2-MSH3 complex, MutSb, is more specialized for larger insertion-deletion loops.

Related Pages

• DNA mismatch repair
• MSH2
• MSH6
• Lynch syndrome
• Colorectal cancer