New roles for RAD52 in DNA repair.
New roles for RAD52 in DNA repair.
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RAD52 在 DNA 修复中的新作用。
DOI：
10.1038/s41422-018-0105-8
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发表时间：
2018
期刊：
影响因子：
44.1
通讯作者：
Greene,EricC
中科院分区：
文献类型：
--
作者：
Xue,Chaoyou;Greene,EricC
转录活性遗传基因座可经受由于R环的形成而产生的DNA双链断裂（DSB）的形成。在最近发表在《细胞》杂志上的一项研究中，Yasuhara及其同事揭示了一种引人注目的新机制，该机制允许细胞通过一种称为转录相关同源重组修复的新修复途径来引导活性基因内的DSB。双链断裂（DSB）是最危险的DNA损伤形式之一，因为它们可以导致人类癌症的标志性染色体重排。转录是DSB的主要来源。1在转录过程中，新生RNA可以与DNA杂交形成R环（图1）。最近的研究揭示了7n R环与同源重组（HR）之间有趣的关系。2-4例如，Ohle等人证明，S.粟酒裂殖酵母需要形成R环2此外，Rad52还能促进S.通过允许细胞使用RNA作为模板来指导DNA修复，从而使酿酒酵母细胞发生突变。最后，Pomerantz及其同事定义了两种RNA指导的DNA修复模式，这两种模式都需要RAD 52。[4]一种机制涉及RNA桥接以协调突触和DNA断裂的连接，第二种机制使用RNA作为模板来逆转录依赖性地替换受损的DNA。4
Transcriptionally active genetic loci can be subject to the formation of DNA double strand breaks (DSBs) that arise due to the formation of R-loops. In a recent study published in Cell, Yasuhara and colleagues have revealed a remarkable new mechanism that allows cells to channel DSBs within active genes through a new repair pathway called transcriptionassociated homologous recombination repair.Double strand breaks (DSBs) are one of the most dangerous forms of DNA damage because they can cause the gross chromosomal rearrangements that are hallmarks of human cancers. Transcription is a leading source of DSBs. 1 During transcription, the nascent RNA can hybridize with the DNA to form R-loops (Fig. 1). Recent studies have revealed intriguing relationships betwee7n R-loops and homologous recombination (HR). 2–4 For instance, Ohle et al. demonstrated that efficient HR in S. pombe actually requires the formation of R-loops. 2 Moreover, Rad52 was found to promote DSB repair in S. cerevisiae by allowing the cells to use the RNA as a template to guide DNA repair. 3 Finally, Pomerantz and colleagues have defined two modes of RNA-directed DNA repair, both of which require RAD52. 4 One mechanism involves RNA bridging to coordinate synapsis and ligation of DNA breaks, and the second mechanism uses RNA as a template for reverse transcription-dependent replacement of damaged DNA. 4