Gene amplification is indicative of progressive genomic instability and thus a common feature of cancerous cells. Mismatch repair proteins like MLH1 and MSH6 are implicated in the removal of DNA replication errors. So far, a deficiency in mismatch repair has been associated with a predisposition to HNPCC, a form of colorectal cancer. The group of Paul Modrich has now shown that the rate of gene amplification is elevated 50- to 100-fold in human cell lines deficient in MLH1 or MSH6, as compared with mismatch-proficient control cells (Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):13802-7). These results illustrate a new role for the mismatch repair proteins in the prevention of gene amplification whose failure may contribute to cancer progression.
Department of Biochemistry, Box 3711
Duke University Medical Center, Durham, NC 27710
Message posted by: Ulrike Sattler
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