MSH2

The MSH2 gene makes a protein that plays an essential role in repairing DNA. This protein fixes mistakes that are made when DNA is copied (replicated) in preparation for cell division. The MSH2 protein uses the energy molecule adenosine triphosphate (ATP) as it performs its work. The MSH2 protein becomes active in the presence of ATP when it is paired with the protein made from either the MSH6 gene or the MSH3 gene. This active protein complex identifies places on the DNA where mistakes have been made during DNA replication. Another group of proteins, the MLH1 protein complex, then takes over to help with the actual repair. The MSH2 gene is a member of a set of genes known as the mismatch repair (MMR) genes.

The following genes are involved in the DNA mismatch repair (MMR) pathway and repair DNA that is not correctly copied before cell division.

• MLH1:mutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli)
• MSH2:mutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli)
• MSH6:mutS homolog 6 (E. coli)
• PMS2:PMS2 postmeiotic segregation increased 2 (S. cerevisiae)

hereditary nonpolyposis colorectal cancer - increased risk from variations of the MSH2 gene

About 40 percent of all cases of hereditary nonpolyposis colorectal cancer (HNPCC) with an identified mutation are associated with mutations in the MSH2 gene. Several hundred MSH2 mutations that predispose people to colorectal cancer and other associated HNPCC cancers have been found. These mutations may cause the production of an abnormally short or inactivated MSH2 protein that can't perform its normal function. When the MSH2 protein is absent or working inadequately, the number of mistakes that are left unrepaired during cell division increases substantially. Errors in DNA accumulate if cells continue to divide, leading to uncontrolled cell growth and the formation of a cancerous tumor.

People with mutations in the MSH2 gene also have an increased chance of developing several other types of cancer, including cancers of the endometrium (lining of the uterus), ovary, stomach, small intestine, liver and gallbladder ducts, upper urinary tract, brain, and skin. Some mutations in the MSH2 gene increase the likelihood of a particular kind of skin tumor in addition to colorectal cancer; this combination is called Muir-Torre syndrome. These rare skin tumors include tumors of skin glands that produce an oily substance called sebum (sebaceous adenomas and carcinomas) and multiple, rapidly growing tumors that usually occur on sun-exposed areas of the skin (keratoacanthomas).

2p22-p21

The MSH2 gene is located on the short (p) arm of chromosome 2 between positions 22 and 21.

See How do geneticists indicate the location of a gene? in the Handbook.

You and your healthcare professional may find the following resources about MSH2 helpful.

• Educational resources - Information pages
  Mismatch Repair Genes hMLH1 and hMSH2 and Colorectal Cancer - CDC fact sheet
• Gene Reviews - Clinical summary
• Gene Tests - DNA tests ordered by healthcare professionals

You may also be interested in these resources, which are designed for genetics professionals and researchers.

• PubMed - Recent literature
• OMIM - Genetic disorder catalog
• Research Resources - Tools for researchers (4 links)

See How are genetic conditions and genes named? in the Handbook.

The Handbook provides basic information about genetics in clear language.

• What is DNA?
• What is a gene?
• How does a gene make a protein?
• How can gene mutations cause disorders?

These links provide additional genetics resources that may be useful.

• Genetics education
• Human Genome Project
• Resources for Genetic Researchers

adenoma ; adenosine triphosphate ; ATP ; cancer ; carcinoma ; cell division ; colon ; colorectal ; DNA ; DNA replication ; duct ; endometrium ; gene ; homologs ; intestine ; keratoacanthoma ; molecule ; mutation ; protein ; segregation ; tumor

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.