关键词: DNA repair RNA polymerase 1 RNA polymerase 2 UV lesions chromatin homeostasis nucleolus

来  源:   DOI:10.1002/1873-3468.14964

Abstract:
The effects of genotoxic agents on DNA and the processes involved in their removal have been thoroughly studied; however, very little is known about the mechanisms governing the reinstatement of cellular activities after DNA repair, despite restoration of the damage-induced block of transcription being essential for cell survival. In addition to impeding transcription, DNA lesions have the potential to disrupt the precise positioning of chromatin domains within the nucleus and alter the meticulously organized architecture of the nucleolus. Alongside the necessity of resuming transcription mediated by RNA polymerase 1 and 2 transcription, it is crucial to restore the structure of the nucleolus to facilitate optimal ribosome biogenesis and ensure efficient and error-free translation. Here, we examine the current understanding of how transcriptional activity from RNA polymerase 2 is reinstated following DNA repair completion and explore the mechanisms involved in reassembling the nucleolus to safeguard the correct progression of cellular functions. Given the lack of information on this vital function, this Review seeks to inspire researchers to explore deeper into this specific subject and offers essential suggestions on how to investigate this complex and nearly unexplored process further.
摘要:
基因毒性剂对DNA的影响及其去除过程已得到彻底研究;然而,对DNA修复后恢复细胞活动的机制知之甚少,尽管恢复损伤诱导的转录阻断对细胞存活至关重要。除了阻碍转录,DNA损伤有可能破坏染色质结构域在细胞核内的精确定位,并改变核仁精心组织的结构。除了需要恢复RNA聚合酶1和2转录介导的转录,至关重要的是恢复核仁的结构,以促进最佳的核糖体生物发生,并确保有效和无错误的翻译。这里,我们研究了目前对DNA修复完成后如何恢复RNA聚合酶2的转录活性的理解,并探索了重组核仁以保护细胞功能正确进展的机制。鉴于缺乏关于这一重要功能的信息,本综述旨在激励研究人员更深入地探索这一特定主题,并就如何进一步研究这一复杂且几乎未探索的过程提供必要的建议。
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