Splitting the yeast centromere by recombination.
Splitting the yeast centromere by recombination.
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DOI：
10.1093/nar/gkad1110
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发表时间：
2024-01-25
影响因子：
14.9
通讯作者：
中科院分区：
文献类型：
--
作者：
尽管已经在癌细胞中通过细胞学观察到了不同人类染色体着丝粒之间的融合，但由于着丝粒是卫星序列的长阵列，因此很难研究这些融合的细节。我们开发了检测酿酒酵母着丝粒内重组（着丝粒间重组）的方法。这些事件在两个活性或两个非活性着丝粒之间以相似的速率（大约 10−8/细胞分裂）发生。我们将大多数重组事件的断点映射到两个着丝粒之间具有 43 个碱基对的不间断同源性区域。通过全基因组 DNA 测序，我们表明大多数（>90%）事件是通过非相互重组（基因转换/断裂诱导的复制）发生的。我们还发现着丝粒间重组可能涉及非同源染色体，产生全臂易位。此外，着丝粒间重组与非常频繁的染色体错误分离有关。这些观察结果支持着丝粒间重组通常具有负面遗传后果的结论。
Although fusions between the centromeres of different human chromosomes have been observed cytologically in cancer cells, since the centromeres are long arrays of satellite sequences, the details of these fusions have been difficult to investigate. We developed methods of detecting recombination within the centromeres of the yeast Saccharomyces cerevisiae (intercentromere recombination). These events occur at similar rates (about 10−8/cell division) between two active or two inactive centromeres. We mapped the breakpoints of most of the recombination events to a region of 43 base pairs of uninterrupted homology between the two centromeres. By whole-genome DNA sequencing, we showed that most (>90%) of the events occur by non-reciprocal recombination (gene conversion/break-induced replication). We also found that intercentromere recombination can involve non-homologous chromosome, generating whole-arm translocations. In addition, intercentromere recombination is associated with very frequent chromosome missegregation. These observations support the conclusion that intercentromere recombination generally has negative genetic consequences.
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