Failure of human mismatch repair has serious consequences, including cancer. One of the most common forms of hereditary cancer is hereditary nonpolyposis colon cancer (HNPCC). Approximately one American in 200 is affected by this disease, and it accounts for about 15% of all colon cancers -- 20,000 cases per year in the United States. One of the characteristics of HNPCC patients is microsatellite instability, which means that DNA microsatellites, tandem repeats of 1- to 4-bp sequences, change in size (number of repeats) during the patient's lifetime. This is unusual; the number of repeats in a given microsatellite may differ from one normal individual to another, but it should be the same in all tissues and remain constant throughout the individual's lifetime. The relationship between microsatellite instability and mismatch repair is that the mismatch repair system is responsible for recognizing and repairing the "bubble" created by the inaccurate insertion of too many or too few copies of a short repeat because of "slippage" during DNA replication. When this system breaks down, such slippage goes unrepaired, leading to mutations in many genes whenever DNA replicates in preparation for cell division. This kind of genetic instability presumably leads to cancer, by mechanisms involving mutated genes (oncogenes and tumor suppressor genes) that are responsible for control of cell division..
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