Defective break-induced replication leads to half-crossovers in Saccharomyces cerevisiae
Defective break-induced replication leads to half-crossovers in Saccharomyces cerevisiae
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DOI：
10.1534/genetics.108.087940
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发表时间：
2008-08-01
期刊：
影响因子：
3.3
通讯作者：
Malkova, Anna
中科院分区：
文献类型：
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作者：
Deem, Angela;Barker, Krista;Malkova, Anna
断裂诱导复制（BIR）是DNA代谢的一个重要过程，它涉及到折叠复制叉的重新启动，以及各种染色体不稳定性，包括杂合性丧失、易位和端粒延长。因此，了解BIR是如何进行和调节的，对于更好地理解真核生物基因组稳定性的维持是很重要的。在这里，我们提出了一个新的酵母实验系统，可以研究BIR的遗传控制。根据对各种dna损伤剂的敏感性对选择的突变进行分析表明，尽管仍然观察到一些与POL32无关的BIR，但删除编码第三个非必需的聚合酶δ亚基的POL32会显著降低BIR的效率。重要的是，pol32 δ细胞中的BIR缺陷与半交叉的形成有关。我们认为这些半交叉是由于BIR中间体的异常加工造成的。此外，我们认为在我们的系统中观察到的半交叉类似于哺乳动物肿瘤细胞中的非互反易位（NRT），因此，我们的系统可能为进一步研究酵母中的NRT机制提供了机会。
Break-induced replication (BIR) is an important process of DNA metabolism that has been implicated in the restart of collapsed replication forks, its well its in various chromosomal instabilities, including loss of heterozygosity, translocations, and alternative telomere lengthening. Therefore, knowledge of how BIR is Carried out and regulated is important for better understanding the maintenance of genomic stability in eukaryotes. Here we present a new yeast experimental system that enables the genetic control of BIR to be investigated. Analysis of mutations selected on the basis of their sensitivity to various DNA-damaging agents demonstrated that deletion of POL32, which encodes a third, nonessential subunit of polymerases delta, significantly reduced the efficiency of BIR, although some POL32-independent BIR was still observed. Importantly, the BIR defect in pol32 Delta cells was associated with the formation of half-crossovers. We propose that these half-crossovers resulted from aberrrant processing of BIR intermediates. Furthermore, we suggest that the half-crossovers observed in our system are analogous to nonreciprocal translocations (NRTs) described in mammalian tumor cells and, thus, our system could represent an oppurtunity to further study the NRT mechnism in yeast.