Inverted repeat-stimulated sister-chromatid exchange events are RAD1-independent but reduced in a msh2 mutant.
Inverted repeat-stimulated sister-chromatid exchange events are RAD1-independent but reduced in a msh2 mutant.
复制标题
反向重复刺激的姐妹染色单体交换事件与 RAD1 无关，但在 msh2 突变体中减少。
DOI：
10.1093/nar/gki835
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发表时间：
2005
影响因子：
14.9
通讯作者：
Tronnes,Ashlie
中科院分区：
文献类型：
--
作者：
Nag,DilipK;Fasullo,Michael;Dong,Zheng;Tronnes,Ashlie
倒置重复序列（IRs）和三核苷酸重复序列（tnr）具有在体内形成二级结构的潜力，已知会导致基因组重排。人类tnr的扩大与几种神经系统疾病有关。IRs和tnr都能刺激酵母自发的不平等姐妹染色单体交换（SCE）。二级结构相关的SCE事件通过双链断裂修复发生。本研究表明，在错配修复基因msh2or msh3突变的菌株中，酵母中自发红外刺激的不相等SCE事件的发生率显著降低，但不受核苷酸切除修复基因geneRAD1突变的影响。在MMR-和rad1突变细胞中，非ir相关的不平等SCE事件增加；然而，含IR和不含IR底物的SCE事件在外背景中发生的水平更高。我们的结果表明自发SCE是通过模板转换机制发生的。与ir一样，tnr已被证明在酵母中产生双链断裂（DSBs）。小鼠TNR扩增依赖于msh2。由于ir介导的SCE事件在msh2细胞中减少，我们提出当使用姐妹或同源物作为模板修复dsb时，会出现TNR扩增突变。
Inverted repeats (IRs) and trinucleotide repeats (TNRs) that have the potential to form secondary structuresin vivoare known to cause genome rearrangements. Expansions of TNRs in humans are associated with several neurological disorders. Both IRs and TNRs stimulate spontaneous unequal sister-chromatid exchange (SCE) in yeast. Secondary structure-associated SCE events occur via double-strand break repair. Here we show that the rate of spontaneous IR-stimulated unequal SCE events in yeast is significantly reduced in strains with mutations in the mismatch repair genesMSH2orMSH3, but unaffected by a mutation in the nucleotide excision-repair geneRAD1. Non-IR-associated unequal SCE events are increased in both MMR- andrad1-mutant cells; however, SCE events for both IR- and non-IR-containing substrates occur at a higher level in theexo1background. Our results suggest that spontaneous SCE occurs by a template switching mechanism. Like IRs, TNRs have been shown to generate double-strand breaks (DSBs) in yeast. TNR expansions in mice areMSH2-dependent. Since IR-mediated SCE events are reduced inmsh2cells, we propose that TNR expansion mutations arise when DSBs are repaired using the sister or the homolog as a template.