Homologous recombination is responsible for cell death in the absence of the Sgs1 and Srs2 helicases
Homologous recombination is responsible for cell death in the absence of the Sgs1 and Srs2 helicases
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DOI：
10.1038/76055
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发表时间：
2000-06-01
期刊：
影响因子：
30.8
通讯作者：
Fabre, F
中科院分区：
文献类型：
--
作者：
Gangloff, S;Soustelle, C;Fabre, F
DNA解旋酶参与DNA代谢的许多方面，包括转录、复制、重组和修复。在酿酒酵母中，Sgs 1解旋酶的缺失导致基因组不稳定和加速老化（1-4）。在人类细胞中，SGS 1直系同源物的突变导致Bloom（BS）。Werner（WS）或Rothmund-Thomson（RTS）综合征，这是一种罕见的常染色体隐性遗传疾病，其特征是与癌症易感性相关的遗传不稳定性（5-7）。虽然有关这些人类疾病的数据正在积累，但对所涉及的蛋白质的功能仍然没有明确的概念。在这里，我们表明，sgs 1三角洲突变体是缺乏DNA修复和有缺陷的诱导重组事件，涉及同源染色体。同源重组的作用在Sgs 1 p和Srs 2 p都不存在的单倍体细胞中得到进一步证明。酵母SRS 2编码参与维持基因组完整性的另一种DNA解旋酶（8-10）。我们的数据表明，在BS中观察到的一些缺陷。WS或RTS是无限制重组的结果。
DNA helicases are involved in many aspects of DNA metabolism, including transcription, replication, recombination and repair. In the yeast Saccharomyces cerevisiae, the absence of the Sgs1 helicase results in genomic instability and accelerated ageing(1-4). In human cells, mutations in orthologues of SGS1 lead to Bloom (BS). Werner (WS) or Rothmund-Thomson (RTS) syndromes, which are rare, autosomal recessive diseases characterized by genetic instability associated with cancer predisposition(5-7). Although data concerning these human diseases are accumulating, there is still no clear idea of the function of the proteins involved. Here we show that sgs1 Delta mutants are deficient in DNA repair and are defective for induced recombination events that involve homologous chromosomes. The role of homologous recombination is further evidenced in haploid cells in which both Sgs1p and Srs2p are absent. Yeast SRS2 encodes another DNA helicase involved in the maintenance of genome integrity(8-10). Our data suggest that some defects observed in BS. WS or RTS are the consequence of unrestrained recombination.