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首页> 外文期刊>Molecular and Cellular Biology >Inverted DNA Repeats Channel Repair of Distant Double-Strand Breaks into Chromatid Fusions and Chromosomal Rearrangements
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Inverted DNA Repeats Channel Repair of Distant Double-Strand Breaks into Chromatid Fusions and Chromosomal Rearrangements

机译：倒置的DNA重复将远距离双链断裂的通道修复成染色单体融合和染色体重排

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摘要

Inverted DNA repeats are known to cause genomic instabilities. Here we demonstrate that double-strand DNA breaks (DSBs) introduced a large distance from inverted repeats in the yeast (Saccharomyces cerevisiae) chromosome lead to a burst of genomic instability. Inverted repeats located as far as 21 kb from each other caused chromosome rearrangements in response to a single DSB. We demonstrate that the DSB initiates a pairing interaction between inverted repeats, resulting in the formation of large dicentric inverted dimers. Furthermore, we observed that propagation of cells containing inverted dimers led to gross chromosomal rearrangements, including translocations, truncations, and amplifications. Finally, our data suggest that break-induced replication is responsible for the formation of translocations resulting from anaphase breakage of inverted dimers. We propose a model explaining the formation of inverted dicentric dimers by intermolecular single-strand annealing (SSA) between inverted DNA repeats. According to this model, anaphase breakage of inverted dicentric dimers leads to gross chromosomal rearrangements (GCR). This “SSA-GCR” pathway is likely to be important in the repair of isochromatid breaks resulting from collapsed replication forks, certain types of radiation, or telomere aberrations that mimic isochromatid breaks.
机译：已知反向DNA重复序列会导致基因组不稳定。在这里，我们证明了双链DNA断裂（DSB）与酵母（）染色体中的反向重复序列相距很远，从而导致基因组不稳定。彼此之间相距21 kb的反向重复序列会导致对单个DSB的染色体重排。我们证明，DSB引发反向重复之间的配对相互作用，导致形成大的双中心反向二聚体。此外，我们观察到含有倒置二聚体的细胞的繁殖会导致总体染色体重排，包括易位，截短和扩增。最后，我们的数据表明，断裂诱导的复制是倒位二聚体后期断裂导致的易位形成的原因。我们提出一个模型解释反向DNA重复之间的分子间单链退火（SSA）形成反向的双着丝二聚体的模型。根据该模型，倒置的双中心二聚体的后期断裂导致总体染色体重排（GCR）。这种“ SSA-GCR”途径可能在修复因复制叉塌陷，某些类型的辐射或模仿异染色质断裂的端粒畸变导致的异染色质断裂的修复中很重要。

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