Department of Human Genetics, Leiden University Medical Center, Einthovenweg 20, 2333ZC, Leiden, the Netherlands.
Department of Human Genetics, Leiden University Medical Center, Einthovenweg 20, 2333ZC, Leiden, the Netherlands.
DNA Repair (Amst). 2019 Oct;82:102686. doi: 10.1016/j.dnarep.2019.102686. Epub 2019 Aug 7.
DNA double-strand breaks (DSBs) affect chromatin integrity and impact DNA-dependent processes such as transcription. Several studies revealed that the transcription of genes located in close proximity to DSBs is transiently repressed. This is achieved through the establishment of either a transient repressive chromatin context or eviction of the RNA polymerase II complex from the damaged chromatin. While these mechanisms of transcription repression have been shown to affect the efficiency and accuracy of DSB repair, it became evident that the transcriptional state of chromatin before DSB formation also influences this process. Moreover, transcription can be initiated from DSB ends, generating long non-coding (lnc)RNAs that will be processed into sequence-specific double-stranded RNAs. These so-called DNA damage-induced (dd)RNAs dictate DSB repair by regulating the accumulation of DNA repair proteins at DSBs. Thus, a complex interplay between mechanisms of transcription activation and repression occurs at DSBs and affects their repair. Here we review our current understanding of the mechanisms that coordinate transcription and DSB repair to prevent genome instability arising from DNA breaks in transcribed regions.
DNA 双链断裂 (DSBs) 会影响染色质的完整性，并影响转录等依赖于 DNA 的过程。多项研究表明，位于 DSB 附近的基因的转录会被短暂抑制。这是通过建立瞬时抑制性染色质环境或从受损染色质中逐出 RNA 聚合酶 II 复合物来实现的。虽然这些转录抑制机制已被证明会影响 DSB 修复的效率和准确性，但很明显，DSB 形成前染色质的转录状态也会影响这一过程。此外，转录可以从 DSB 末端起始，产生将被加工成序列特异性双链 RNA 的长非编码 (lnc)RNA。这些所谓的 DNA 损伤诱导 (dd)RNA 通过调节 DNA 修复蛋白在 DSB 处的积累来调控 DSB 修复。因此，在 DSB 处发生转录激活和抑制机制之间的复杂相互作用，并影响它们的修复。在这里，我们回顾了我们对协调转录和 DSB 修复以防止源自转录区域 DNA 断裂的基因组不稳定性的机制的现有理解。
