title: DNA mismatch repair and Lynch syndrome.
abstract: The evolutionary conserved mismatch repair proteins correct a wide range of DNA replication errors. Their importance as guardians of genetic integrity is reflected by the tremendous decrease of replication fidelity (two to three orders of magnitude) conferred by their loss. Germline mutations in mismatch repair genes, predominantly MSH2 and MLH1, have been found to underlie the Lynch syndrome (also called hereditary non-polyposis colorectal cancer, HNPCC), a hereditary predisposition for cancer. Lynch syndrome affects predominantly the colon and accounts for 2-5% of all colon cancer cases. During more than 30 years of biochemical, crystallographic and clinical research, deep insight has been achieved in the function of mismatch repair and the diseases that are associated with its loss. We review the biochemistry of mismatch repair and also introduce the clinical, diagnostic and genetic aspects of Lynch syndrome.
authors.affiliation: Klinik für Innere Medizin II, Universitätsklinikum des Saarlandes, Kirrberger Strasse, Gebäude 41, D-66421 Homburg, Germany. guido.plotz@uniklinik-saarland.de
authors.forename: Guido
authors.initials: G
authors.lastname: Plotz
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.forename: Jochen
authors.initials: J
authors.lastname: Raedle
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000235:genetics; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis / Q000235:genetics*; D053843:DNA Mismatch Repair; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics; D006801:Humans; D053842:Microsatellite Instability; D008957:Models, Genetic; D000070956:MutL Proteins; D051719:MutS DNA Mismatch-Binding Protein / Q000737:chemistry / Q000235:genetics
chemical_list: D029968:Escherichia coli Proteins; C074770:MutL protein, E coli; D000251:Adenosine Triphosphatases; D000070956:MutL Proteins; D051719:MutS DNA Mismatch-Binding Protein