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首页> 外文期刊>Molecular and Cellular Biology >SIR Functions Are Required for the Toleration of an Unrepaired Double-Strand Break in a Dispensable Yeast Chromosome
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SIR Functions Are Required for the Toleration of an Unrepaired Double-Strand Break in a Dispensable Yeast Chromosome

机译：SIR功能是必需的，可耐受可分配酵母染色体中未修复的双链断裂。

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Unrepaired DNA double-strand breaks (DSBs) typically result in G2 arrest. Cell cycle progression can resume following repair of the DSBs or through adaptation to the checkpoint, even if the damage remains unrepaired. We developed a screen for factors in the yeast Saccharomyces cerevisiae that affect checkpoint control and/or viability in response to a single, unrepairable DSB that is induced by HO endonuclease in a dispensable yeast artificial chromosome containing human DNA. SIR2, -3, or -4 mutants exhibit a prolonged,RAD9-dependent G2 arrest in response to the unrepairable DSB followed by a slow adaptation to the persistent break, leading to division and rearrest in the next G2. There are a small number of additional cycles before permanent arrest as microcolonies. Thus, SIR genes, which repress silent mating type gene expression, are required for the adaptation and the prevention of indirect lethality resulting from an unrepairable DSB in nonessential DNA. Rapid adaptation to the G2 checkpoint and high viability were restored insir ? strains containing additional deletions of the silent mating type loci HMLand HMR, suggesting that genes under mating type control can reduce the toleration of a single DSB. However, coexpression ofMATa1 and MATα2 in Sir+ haploid cells did not lead to lethality from the HO-induced DSB, suggesting that toleration of an unrepaired DSB requires more than one Sir+ function.
机译：未修复的DNA双链断裂（DSB）通常导致G 2 停滞。即使损伤未修复，DSB修复后或通过适应检查点仍可恢复细胞周期进程。我们开发了一种筛选酵母 Saccharomyces cerevisiae 中的因素的方法，这些因素会影响HO内切核酸酶在含有人DNA的可分配酵母人工染色体中诱导的单个不可修复的DSB的反应，从而影响检查点控制和/或生存能力。 SIR2 ，- 3 或- 4 突变体表现出延长的 RAD9 依赖性G 2 < / sub>因无法修复的DSB而被逮捕，随后缓慢适应持续性断裂，导致下一个G 2 分裂并重新起步。在永久逮捕之前，有少量其他周期可以作为微殖民地。因此，抑制非沉默交配型基因表达的 SIR 基因是适应性和防止非必需DNA中不可修复的DSB导致的间接致死力所必需的。在 sir ？菌株中恢复了对G 2 检查点的快速适应性和高生存力，该菌株含有沉默交配型基因座 HML的其他缺失和 HMR ，表明在交配类型控制下的基因可以降低单个DSB的耐受性。然而，Sir + 单倍体细胞中 MAT a1和 MAT α2的共表达并没有导致HO诱导的DSB致死，这表明耐受性未修复的DSB中，需要多个Sir + 函数。

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