DNA错配修复与癌症

DNA mismatch repair and cancer.

作者信息

Prolla T A

机构信息

Department of Genetics, University of Wisconsin-Madison 53706, USA.

出版信息

Curr Opin Cell Biol. 1998 Jun;10(3):311-6. doi: 10.1016/s0955-0674(98)80005-7.

DOI:10.1016/s0955-0674(98)80005-7

PMID:9640530

Abstract

Mutations in DNA mismatch repair (MMR) genes have been associated with hereditary nonpolyposis colorectal cancer. Studies in bacteria, yeast and mammals suggest that the basic components of the MMR system are evolutionarily conserved, but studies in eukaryotes also imply novel functions for MMR proteins. Recent results suggest that mutations in MMR genes lead to tumorigenesis in mice, but DNA replication errors appear to be insufficient to initiate intestinal tumorigenesis in this model system. Additionally, MMR-deficient cell lines display a mutator phenotype and resistance to several cytotoxic agents, including compounds widely used in cancer chemotherapy.

摘要

DNA错配修复（MMR）基因的突变与遗传性非息肉病性结直肠癌相关。对细菌、酵母和哺乳动物的研究表明，MMR系统的基本组成部分在进化上是保守的，但对真核生物的研究也暗示了MMR蛋白的新功能。最近的结果表明，MMR基因的突变会导致小鼠肿瘤发生，但在该模型系统中，DNA复制错误似乎不足以引发肠道肿瘤发生。此外，MMR缺陷的细胞系表现出突变表型，并对几种细胞毒性药物具有抗性，包括癌症化疗中广泛使用的化合物。