Fishel R, Wilson T
DNA Repair and Molecular Carcinogenesis Program, Kimmel Cancer Institute and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Curr Opin Genet Dev. 1997 Feb;7(1):105-13. doi: 10.1016/s0959-437x(97)80117-7.
Alterations of the human mismatch repair genes have been linked to hereditary non-polyposis colon cancer (HNPCC) as well as to sporadic cancers that exhibit microsatellite instability. The human mismatch repair genes are highly conserved homologs of the Escherichia coli MutHLS system. Six MutS homologs have been identified in Saccharomyces cerevisiae and four MutS homologs have been identified in human cells. At least three of these eukaryotic MutS homologs are involved in the recognition/binding of mispaired nucleotides and nucleotide lesions. MSH2 plays a fundamental role in mispair recognition whereas MSH3 and MSH6 appear to modify the specificity of this recognition. The redundant functions of MSH3 and MSH6 explain the greater prevalence of hmsh2 mutations in HNPCC families.
人类错配修复基因的改变与遗传性非息肉病性结直肠癌（HNPCC）以及表现出微卫星不稳定性的散发性癌症有关。人类错配修复基因是大肠杆菌MutHLS系统的高度保守同源物。在酿酒酵母中已鉴定出六个MutS同源物，在人类细胞中已鉴定出四个MutS同源物。这些真核MutS同源物中至少有三个参与错配核苷酸和核苷酸损伤的识别/结合。MSH2在错配识别中起基本作用，而MSH3和MSH6似乎改变了这种识别的特异性。MSH3和MSH6的冗余功能解释了HNPCC家族中hmsh2突变的更高发生率。
