Microsatellite instability in yeast: Dependence on repeat unit size and DNA mismatch repair genes

Microsatellite instability in yeast: Dependence on repeat unit size and DNA mismatch repair genes
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DOI:
10.1128/mcb.17.5.2851
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发表时间:
1997-05-01
影响因子:
5.3
通讯作者:
Petes, TD
Petes, TD
中科院分区:
生物学2区
文献类型:
--
作者:
Sia, EA;Kokoska, RJ;Petes, TD

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被引文献

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我们检查了缺乏 DNA 错配修复的酿酒酵母菌株中不同重复单位长度的微卫星的稳定性。 msh2 和 msh3 突变使重复单元为 1、2、4、5 和 8 bp 的微卫星不稳定; msh2 突变使 18 bp 的多聚 (G) 片段不稳定数千倍,而 msh3 突变则不稳定约 100 倍。 msh6 突变使具有 1 和 2 bp 重复单元的微卫星不稳定,但对具有较大重复单元的微卫星没有影响。这些结果表明编码序列含有重复DNA。束将成为具有错配修复缺陷的人类肿瘤突变的首选靶位点。我们发现DNA错配修复基因使重复单元为1至13 bp的微卫星不稳定,但对重复单元为16或20 bp的小卫星的稳定性没有影响。我们的数据还表明,由于 DNA 聚合酶滑移而导致的新生链上的移位环的修复方式与模板链上的环不同。
We examined the stability of microsatellites of different repeat unit lengths in Saccharomyces cerevisiae strains deficient in DNA mismatch repair. The msh2 and msh3 mutations destabilized microsatellites with repeat units of 1, 2, 4, 5, and 8 bp; a poly(G) tract of 18 bp was destabilized several thousand-fold by the msh2 mutation and about 100-fold by msh3. The msh6 mutations destabilized microsatellites with repeat units of 1 and 2 bp but had no effect on microsatellites with larger repeats. These results argue that coding sequences containing repetitive DNA. tracts will be preferred target sites for mutations in human tumors with mismatch repair defects. We find that the DNA mismatch repair genes destabilize microsatellites with repeat units from 1 to 13 bp but have no effect on the stability of minisatellites with repeat units of 16 or 20 bp. Our data also suggest that displaced loops on the nascent strand, resulting from DNA polymerase slippage, are repaired differently than loops on the template strand.