Saccharomyces cerevisiae rad51 mutants are defective in DNA damage-associated sister chromatid exchanges but exhibit increased rates of homology-directed translocations.
Saccharomyces cerevisiae rad51 mutants are defective in DNA damage-associated sister chromatid exchanges but exhibit increased rates of homology-directed translocations.
复制标题
酿酒酵母 rad51 突变体在 DNA 损伤相关的姐妹染色单体交换中存在缺陷，但表现出同源定向易位率增加。
DOI：
10.1093/genetics/158.3.959
复制
发表时间：
2001
期刊：
影响因子：
3.3
通讯作者：
Bennett,T
中科院分区：
文献类型：
--
作者：
Fasullo,M;Giallanza,P;Dong,Z;Cera,C;Bennett,T
酿酒酵母（Saccharomyces cerevisiaeRad51）在结构上与大肠杆菌（escherichia coli）相似。我们研究了s。DNA损伤相关的不相等姐妹染色单体交换（SCEs）、易位和倒位。这些重排的频率是通过监测两个his3片段his3-Δ5 ‘和his3-Δ3 ’：：HOcs之间的有丝分裂重组来测量的，当定位在不同的染色体上或串联在一起时，定向为正方向或反向方向。细胞暴露于化学试剂和辐射以及HO内切酶酶切athis3-Δ3 '::HOcs后测定重组。野生型和rad51突变株在自发性SCEs发生率上无差异；然而，在therad51突变体中，自发反转率降低了三倍。当细胞暴露于辐射或化学DNA损伤剂或当HO内切酶诱导的双链断裂（DSBs）直接靶向athis3-Δ3 '::HOcs时，Therad51null突变体在DNA损伤相关的SCE中存在缺陷。在rad51突变体中，DNA损伤相关的SCEs缺陷与二倍体株中8倍高的自发定向易位水平和更高水平的辐射相关易位相关。我们建议这样做。酿酒酵母rad51通过减少由rad51非依赖性断裂诱导复制（BIR）机制产生的非互易易位来促进基因组稳定性。
Saccharomyces cerevisiaeRad51 is structurally similar toEscherichia coliRecA. We investigated the role ofS. cerevisiae RAD51in DNA damage-associated unequal sister chromatid exchanges (SCEs), translocations, and inversions. The frequency of these rearrangements was measured by monitoring mitotic recombination between twohis3fragments,his3-Δ5′ andhis3-Δ3′::HOcs, when positioned on different chromosomes or in tandem and oriented in direct or inverted orientation. Recombination was measured after cells were exposed to chemical agents and radiation and after HO endonuclease digestion athis3-Δ3′::HOcs. Wild-type andrad51mutant strains showed no difference in the rate of spontaneous SCEs; however, the rate of spontaneous inversions was decreased threefold in therad51mutant. Therad51null mutant was defective in DNA damage-associated SCE when cells were exposed to either radiation or chemical DNA-damaging agents or when HO endonuclease-induced double-strand breaks (DSBs) were directly targeted athis3-Δ3′::HOcs. The defect in DNA damage-associated SCEs inrad51mutants correlated with an eightfold higher spontaneous level of directed translocations in diploid strains and with a higher level of radiation-associated translocations. We suggest thatS. cerevisiae RAD51facilitates genomic stability by reducing nonreciprocal translocations generated byRAD51-independent break-induced replication (BIR) mechanisms.