Fishel R, Kolodner R D
Department of Microbiology and Molecular Genetics, Markey Center for Molecular Genetics, University of Vermont School of Medicine, Burlington 05405, USA.
Curr Opin Genet Dev. 1995 Jun;5(3):382-95. doi: 10.1016/0959-437x(95)80055-7.
Mismatched base pairs are generated by damage to DNA, by damage to nucleotide precursors, by errors that occur during DNA replication, and during the formation of intermediates in genetic recombination. Enzyme systems that faithfully repair these DNA aberrations have been identified in a wide variety of organisms. At lease some of the components of these repair systems have been conserved, both structurally and functionally, throughout evolutionary time. In humans, defective mismatch repair genes have been linked to hereditary nonpolyposis colon cancer as well as to sporadic cancers that exhibit length polmorphisms in simple repeat (microsatellite) DNA sequences. The involvement of mismatch repair defects in microsatellite instability and tumorigenesis suggests that a generalized mutator phenotype is responsible for the large number of genetic alterations observed in tumors.
错配碱基对可由DNA损伤、核苷酸前体损伤、DNA复制过程中发生的错误以及基因重组中间体形成过程中产生。在多种生物体中已鉴定出能忠实地修复这些DNA异常的酶系统。在整个进化过程中，这些修复系统的至少某些组分在结构和功能上都得到了保守。在人类中，缺陷的错配修复基因已与遗传性非息肉病性结肠癌以及在简单重复（微卫星）DNA序列中表现出长度多态性的散发性癌症相关联。错配修复缺陷与微卫星不稳定性及肿瘤发生之间的关联表明，一种普遍的突变体表型是肿瘤中观察到的大量基因改变的原因。
