MSOP

MSH3

MSH3 (MutS Homolog 3) is a human gene that encodes a protein involved in the DNA mismatch repair (MMR) system. This system is crucial for maintaining genomic stability by correcting DNA replication errors. MSH3 forms a heterodimer with MSH2, another MMR protein, to recognize and repair insertion-deletion loops and other mismatches in DNA.

Structure

The MSH3 protein is a member of the MutS family of proteins, which are highly conserved across species. The protein consists of several domains, including an ATPase domain and a DNA-binding domain. These domains are essential for its function in mismatch repair.

Function

MSH3, in conjunction with MSH2, forms the MutSβ complex. This complex is specifically involved in the repair of insertion-deletion loops, which are common errors that occur during DNA replication. The MutSβ complex recognizes these errors and initiates the repair process by recruiting other proteins involved in the MMR pathway, such as MLH1 and PMS2.

Clinical Significance

Mutations in the MSH3 gene can lead to defects in the mismatch repair system, contributing to genomic instability and increasing the risk of certain types of cancer. While MSH3 mutations are less commonly associated with hereditary nonpolyposis colorectal cancer (HNPCC) compared to mutations in other MMR genes like MLH1 and MSH2, they can still play a role in cancer development.

Research and Implications

Research into MSH3 and its role in DNA repair continues to be an important area of study, particularly in understanding its contribution to cancer biology. Studies have shown that MSH3 deficiency can lead to microsatellite instability, a hallmark of certain cancers, including colorectal and endometrial cancers.

Also see

• DNA mismatch repair
• MSH2
• MLH1
• PMS2
• Microsatellite instability