Plotz Guido, Zeuzem Stefan, Raedle Jochen
Klinik für Innere Medizin II, Universitätsklinikum des Saarlandes, Kirrberger Strasse, Gebäude 41, D-66421 Homburg, Germany.
J Mol Histol. 2006 Sep;37(5-7):271-83. doi: 10.1007/s10735-006-9038-5. Epub 2006 Jul 4.
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.
进化上保守的错配修复蛋白可纠正多种DNA复制错误。它们作为遗传完整性守护者的重要性体现在，其缺失会导致复制保真度大幅下降（两到三个数量级）。错配修复基因的种系突变，主要是MSH2和MLH1，已被发现是林奇综合征（也称为遗传性非息肉病性结直肠癌，HNPCC）的病因，这是一种遗传性癌症易感性疾病。林奇综合征主要影响结肠，占所有结肠癌病例的2%-5%。在30多年的生物化学、晶体学和临床研究中，我们对错配修复的功能及其缺失相关疾病有了深入了解。我们回顾了错配修复的生物化学，还介绍了林奇综合征的临床、诊断和遗传学方面。
