The Role of Replication-Associated Repair Factors on R-Loops.

The Role of Replication-Associated Repair Factors on R-Loops.
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DOI:
10.3390/genes8070171
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发表时间:
2017-06-27
期刊:
影响因子:
3.5
通讯作者:
Gómez-González B
Gómez-González B
中科院分区:
生物学3区
文献类型:
--
作者:
Bhatia V;Herrera-Moyano E;Aguilera A;Gómez-González B

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新生的RNA可以重新侵入DNA双螺旋以形成称为R环的结构,其中单链DNA(ssDNA)伴随着DNA-RNA杂合体。未解决的R环可以阻碍转录和复制过程,并通过尚未完全理解的机制导致基因组不稳定。在这个意义上,R环和某些染色质标记之间的连接已经被报道,可能在R环稳态和基因组不稳定性中发挥关键作用。为了抵消R环的潜在有害作用,不同的保守信使核糖核蛋白(mRNP)生物发生和核输出因子阻止R环的形成,而普遍表达的特异性核糖核酸酶和DNA-RNA解旋酶解决DNA-RNA杂合体。然而,与R环传感和加工相关的分子事件尚不清楚。鉴于R环阻碍复制进程,一些DNA复制相关因素可能有助于溶解R环或防止R环介导的基因组不稳定性。为了支持这一点,R环在BRCA 1、BRCA 2或范可尼贫血(FA)DNA修复因子耗尽的细胞中积累,表明它们在R环溶解中起着积极作用。根据这些结果,我们回顾了我们目前对复制相关DNA修复途径在防止R环有害后果中的作用的看法。
The nascent RNA can reinvade the DNA double helix to form a structure termed the R-loop, where a single-stranded DNA (ssDNA) is accompanied by a DNA-RNA hybrid. Unresolved R-loops can impede transcription and replication processes and lead to genomic instability by a mechanism still not fully understood. In this sense, a connection between R-loops and certain chromatin markers has been reported that might play a key role in R-loop homeostasis and genome instability. To counteract the potential harmful effect of R-loops, different conserved messenger ribonucleoprotein (mRNP) biogenesis and nuclear export factors prevent R-loop formation, while ubiquitously-expressed specific ribonucleases and DNA-RNA helicases resolve DNA-RNA hybrids. However, the molecular events associated with R-loop sensing and processing are not yet known. Given that R-loops hinder replication progression, it is plausible that some DNA replication-associated factors contribute to dissolve R-loops or prevent R-loop mediated genome instability. In support of this, R-loops accumulate in cells depleted of the BRCA1, BRCA2 or the Fanconi anemia (FA) DNA repair factors, indicating that they play an active role in R-loop dissolution. In light of these results, we review our current view of the role of replication-associated DNA repair pathways in preventing the harmful consequences of R-loops.
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