Prolla T A, Abuin A, Bradley A
Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA.
Semin Cancer Biol. 1996 Oct;7(5):241-7. doi: 10.1006/scbi.1996.0032.
Biochemical and genetic approaches have been used to demonstrate that basic elements of a DNA mismatch repair (MMR) pathway are conserved between bacteria, yeast and mammals. Recently, mutations in the human MMR genes MSH2, MLH1, PMS1 and PMS2 have been implicated in a common form of hereditary colon cancer and in sporadic tumors of various tissues. In order to better understand the consequences of MMR deficiency in mammalian organisms, mice deficient for the Pms2, Mlh1 and Msh2 MMR gene homologues have been generated. MMR deficient mice display a general increase in spontaneous mutation rate and develop tumors during the first year of life. Additionally, loss of MMR appears to accelerate tumorigenesis in an Apc deficient background.
生物化学和遗传学方法已被用于证明DNA错配修复（MMR）途径的基本元件在细菌、酵母和哺乳动物之间是保守的。最近，人类MMR基因MSH2、MLH1、PMS1和PMS2的突变与一种常见的遗传性结肠癌以及各种组织的散发性肿瘤有关。为了更好地理解MMR缺陷在哺乳动物中的后果，已培育出Pms2、Mlh1和Msh2 MMR基因同源物缺陷的小鼠。MMR缺陷的小鼠自发突变率普遍增加，并在出生后的第一年内发生肿瘤。此外，在Apc缺陷的背景下，MMR的缺失似乎会加速肿瘤发生。
