Replication Fork Protection Factors Controlling R-Loop Bypass and Suppression.
Replication Fork Protection Factors Controlling R-Loop Bypass and Suppression.
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DOI：
10.3390/genes8010033
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发表时间：
2017-01-14
期刊：
影响因子：
3.5
通讯作者：
Stirling PC
中科院分区：
文献类型：
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作者：
Chang EY;Stirling PC
多年来，复制-转录冲突一直是基因组不稳定性的一个被充分研究的来源，并且经常与RNA加工中的缺陷有关。然而，最近对复制叉相关蛋白的表征表明，叉保护中的缺陷可以直接或间接地稳定基因组中的R环结构，并促进导致基因组不稳定的转录-复制冲突。基本的DNA复制相关活动如拓扑异构酶或微型染色体维持（MCM）解旋酶复合物的缺陷，以及叉相关的保护因子如范可尼贫血途径，似乎都可以减轻转录-复制冲突。在这里，我们将强调最近的进展，支持的概念，正常和强大的复制体功能本身是一个关键组成部分，减轻R环耦合基因组的不稳定性。
Replication–transcription conflicts have been a well-studied source of genome instability for many years and have frequently been linked to defects in RNA processing. However, recent characterization of replication fork-associated proteins has revealed that defects in fork protection can directly or indirectly stabilize R-loop structures in the genome and promote transcription–replication conflicts that lead to genome instability. Defects in essential DNA replication-associated activities like topoisomerase, or the minichromosome maintenance (MCM) helicase complex, as well as fork-associated protection factors like the Fanconi anemia pathway, both appear to mitigate transcription–replication conflicts. Here, we will highlight recent advances that support the concept that normal and robust replisome function itself is a key component of mitigating R-loop coupled genome instability.