Both CAG repeats and inverted DNA repeats stimulate spontaneous unequal sister-chromatid exchange in Saccharomyces cerevisiae.
Both CAG repeats and inverted DNA repeats stimulate spontaneous unequal sister-chromatid exchange in Saccharomyces cerevisiae.
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DOI：
10.1093/nar/gkh901
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发表时间：
2004
影响因子：
14.9
通讯作者：
D. Nag;Manisha Suri;E. Stenson
中科院分区：
文献类型：
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作者：
D. Nag;Manisha Suri;E. Stenson
含有三核苷酸重复（TNR）的基因组区域高度不稳定，因为重复序列表现出高频率的突变变化，其中它们经历重复次数的收缩或扩展。尽管 TNR 的扩增与多种人类遗传疾病有关，但其扩增机制却知之甚少。对模型生物体的广泛研究表明，TNR 的不稳定性是通过多种机制发生的，包括复制滑移、DNA 修复和重组。在所有模型中，疾病相关 TNR 形成二级结构是突变过程中的关键步骤。在本报告中，我们证明 TNR 和反向重复序列 (IR) 都有可能在体内形成二级结构，增加营养生长酵母细胞中自发的不等姐妹染色单体交换 (SCE)。我们的结果还表明，TNR 介导的 SCE 事件独立于 RAD50、MRE11 和 RAD51，而 IR 刺激的 SCE 依赖于 RAD52 上位基团基因。我们认为许多 TNR 扩展突变是由 SCE 发生的。
Genomic regions containing trinucleotide repeats (TNRs) are highly unstable, as the repeated sequences exhibit a high rate of mutational change, in which they undergo either a contraction or an expansion of repeat numbers. Although expansion of TNRs is associated with several human genetic diseases, the expansion mechanism is poorly understood. Extensive studies in model organisms have indicated that instability of TNRs occurs by several mechanisms, including replication slippage, DNA repair and recombination. In all models, the formation of secondary structures by disease-associated TNRs is a critical step in the mutation process. In this report, we demonstrate that TNRs and inverted repeats (IRs) both of which have the potential to form secondary structures in vivo, increase spontaneous unequal sister-chromatid exchange (SCE) in vegetatively growing yeast cells. Our results also show that TNR-mediated SCE events are independent of RAD50, MRE11 and RAD51, whereas IR-stimulated SCEs are dependent on the RAD52 epistasis-group genes. We propose that many TNR expansion mutations occur by SCE.