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Mapping of mitotic gene conversion tracts associated with repair of a defined double-strand break (DSB) using SNP microarray

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Mitotic recombination between homologous chromosomes can lead to loss-of-heterozygosity (LOH), which is an important contributor to human disease. In the current study, a defined double-strand break (DSB) on chromosome IV was used to initiate LOH in a yeast strain with sequence-diverged chromosomes. Associated gene conversion tracts, which reflect the repair of mismatches formed when diverged chromosomes exchange single strands, were mapped using microarrays. LOH events reflected two broken chromosomes, one of which was repaired as a crossover and the other as a noncrossover.

同源染色体间的有丝分裂重组可引发杂合性缺失(loss-of-heterozygosity, LOH),该现象是人类疾病的重要致病诱因之一。本研究通过在携带序列分化染色体的酵母菌株的四号染色体上引入特异性双链断裂(double-strand break, DSB),以启动LOH的发生。当分化的染色体发生单链交换时会形成错配结构,研究团队利用微阵列技术对可反映该错配修复过程的相关基因转换轨迹进行了定位分析。结果显示,LOH事件涉及两条断裂的染色体,其中一条以重组交换的方式完成修复,另一条则以非交换的方式完成修复。

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