REQUIREMENT OF THE YEAST RTH1 5' TO 3' EXONUCLEASE FOR THE STABILITY OF SIMPLE REPETITIVE DNA
REQUIREMENT OF THE YEAST RTH1 5' TO 3' EXONUCLEASE FOR THE STABILITY OF SIMPLE REPETITIVE DNA
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DOI：
10.1126/science.7618086
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发表时间：
1995-07-14
期刊：
影响因子：
56.9
通讯作者：
PRAKASH, S
中科院分区：
文献类型：
--
作者：
JOHNSON, RE;KOVVALI, GK;PRAKASH, S
简单重复的DNA序列在人类结直肠癌和各种其他癌症中是不稳定的。DNA错配修复基因MSH 2、MLH 1和PMS 1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，编码5'至3'核酸外切酶的酵母RTH 1基因中的无效突变被证明使简单重复DNA的不稳定率增加多达280倍，并使自发突变率增加30倍。上位性分析与RTH 1编码的核酸酶在MSH 2-MLH 1-PMS 1错配修复途径中起作用的假设一致。
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-MLH1-PMS1 mismatch repair pathway.