Johnson R E, Kovvali G K, Prakash L, Prakash S
Center for Molecular Science, University of Texas Medical Branch, Galveston 77555-1061, USA.
Science. 1995 Jul 14;269(5221):238-40. doi: 10.1126/science.7618086.
Simple repetitive DNA sequences are unstable in human colorectal cancers and a variety of other cancers. Mutations in the DNA mismatch repair genes MSH2, MLH1, and PMS1 result in elevated rates of spontaneous mutation and cause a marked increase in the instability of simple repeats. Compared with the wild type, a null mutation in the yeast RTH1 gene, which encodes a 5' to 3' exonuclease, was shown to increase the rate of instability of simple repetitive DNA by as much as 280 times and to increase the spontaneous mutation rate by 30 times. Epistasis analyses were consistent with the hypothesis that this RTH1-encoded nuclease has a role in the MSH2-MLH-1-PMS1 mismatch repair pathway.
简单重复DNA序列在人类结直肠癌和多种其他癌症中不稳定。DNA错配修复基因MSH2、MLH1和PMS1中的突变导致自发突变率升高，并导致简单重复序列的不稳定性显著增加。与野生型相比，酵母RTH1基因（编码一种5'至3'核酸外切酶）中的无效突变显示出简单重复DNA的不稳定性增加了280倍，自发突变率增加了30倍。上位性分析与该RTH1编码的核酸酶在MSH2-MLH-1-PMS1错配修复途径中起作用的假设一致。
