Most meiotic CAG repeat tract-length alterations in yeast are SP011 dependent

Most meiotic CAG repeat tract-length alterations in yeast are SP011 dependent
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DOI:
10.1007/s00438-001-0635-4
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发表时间:
2002-03-01
影响因子:
3.1
通讯作者:
Nag, DK
Nag, DK
中科院分区:
生物学3区
文献类型:
--
作者:
Jankowski, C;Nag, DK

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早期的研究认为,与遗传性神经系统疾病相关的三核苷酸重复序列的扩增是由于DNA复制中的错误。然而,最近的研究表明,重组可能在三重重复扩增中发挥重要作用。CAG重复序列在酵母减数分裂中诱导双链断裂,而双链断裂的形成依赖于减数分裂的重组机制。减数分裂不稳定的比率是有丝分裂不稳定的几倍。为了确定DSB修复是否是负责高重复序列长度的变化率,减数分裂重复序列不稳定的频率进行了比较,在野生型和spo11突变株。在spo11背景下,减数分裂重复道不稳定性的速率保持在有丝分裂水平。提示酵母中CAG重复序列的减数分裂改变是通过重组机制发生的。其中几个减数分裂片段长度的改变是由于DSB修复涉及使用姐妹染色单体作为模板。
The expansion of trinucleotide repeat sequences associated with hereditary neurological diseases is believed from earlier studies to be due to errors in DNA replication. However, more recent studies have indicated that recombination may play a significant role in triplet repeat expansion. CAG repeat tracts have been shown to induce double-strand breaks (DSBs) during meiosis in yeast, and DSB formation is dependent on the meiotic recombination machinery. The rate of meiotic instability is several fold higher than mitotic instability. To determine whether DSB repair is responsible for the high rate of repeat tract-length alterations, the frequencies of meiotic repeat-tract instability were compared in wild-type and spo11 mutant strains. In the spo11 background, the rate of meiotic repeat-tract instability remained at the mitotic level. suggesting that meiotic alterations of CAG repeat tracts in yeast occur by the recombination mechanism. Several of these meiotic tract-length alterations are due to DSB repair involving use of the sister chromatid as a template.