Rad51 inhibits translocation formation by non-conservative homologous recombination in Saccharomyces cerevisiae.
Rad51 inhibits translocation formation by non-conservative homologous recombination in Saccharomyces cerevisiae.
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DOI：
10.1371/journal.pone.0011889
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发表时间：
2010-07-29
期刊：
影响因子：
3.7
通讯作者：
Bailis AM
中科院分区：
文献类型：
--
作者：
Manthey GM;Bailis AM
染色体易位是电离辐射（IR）暴露的主要生物学反应，可能是由DNA双链断裂（DSB）的不适当修复引起的。真核生物基因组中丰富的重复序列为通过非等位重复序列之间的同源重组（HR）修复此类断裂提供了充足的机会。有趣的是，在芽殖酵母中，酿酒酵母（Saccharomyces cerevisiae）的中心链交换蛋白Rad51（其是通过保持基因组结构的未连接重复之间的基因转换进行DSB修复所需的）也通过几种HR机制抑制易位形成。特别是，Rad51通过单链退火（SSA）抑制易位形成，这可能是酵母和哺乳动物细胞中HR易位形成的最有效机制。此外，增强易位的形成，出现在Rad51的情况下，显示出独特的模式的遗传控制，这表明这是通过一个单独的机制发生。由于哺乳动物细胞中RAD51的亚型突变也通过保守基因转换减少DSB修复，并通过SSA刺激非保守修复，因此这种机制也可能在人类中起作用，并可能导致基因组不稳定性，从而推动癌症的发展。
Chromosomal translocations are a primary biological response to ionizing radiation (IR) exposure, and are likely to result from the inappropriate repair of the DNA double-strand breaks (DSBs) that are created. An abundance of repetitive sequences in eukaryotic genomes provides ample opportunity for such breaks to be repaired by homologous recombination (HR) between non-allelic repeats. Interestingly, in the budding yeast, Saccharomyces cerevisiae the central strand exchange protein, Rad51 that is required for DSB repair by gene conversion between unlinked repeats that conserves genomic structure also suppresses translocation formation by several HR mechanisms. In particular, Rad51 suppresses translocation formation by single-strand annealing (SSA), perhaps the most efficient mechanism for translocation formation by HR in both yeast and mammalian cells. Further, the enhanced translocation formation that emerges in the absence of Rad51 displays a distinct pattern of genetic control, suggesting that this occurs by a separate mechanism. Since hypomorphic mutations in RAD51 in mammalian cells also reduce DSB repair by conservative gene conversion and stimulate non-conservative repair by SSA, this mechanism may also operate in humans and, perhaps contribute to the genome instability that propels the development of cancer.
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影响因子：
14.9
作者：
Colavito S;Macris-Kiss M;Seong C;Gleeson O;Greene EC;Klein HL;Krejci L;Sung P
通讯作者：
Sung P
DOI：
10.1016/j.cub.2009.05.057
发表时间：
2009-07-14
期刊：
Current biology : CB
影响因子：
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作者：
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通讯作者：
Venkitaraman AR
影响因子：
56.9
作者：
BARDWELL, AJ;BARDWELL, L;FRIEDBERG, EC
通讯作者：
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影响因子：
56.9
作者：
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通讯作者：
HABER, JE
影响因子：
5.3
作者：
FASULLO, MT;DAVIS, RW
通讯作者：
DAVIS, RW