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从沉默到交响乐:DNA损伤应答中的转录抑制与恢复

From silence to symphony: transcriptional repression and recovery in response to DNA damage.

作者信息

Ajit Kamal, Gullerova Monika

机构信息

Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.

出版信息

Transcription. 2024 Jun-Oct;15(3-5):161-175. doi: 10.1080/21541264.2024.2406717. Epub 2024 Oct 1.

Abstract

Genotoxic stress resulting from DNA damage is resolved through a signaling cascade known as the DNA Damage Response (DDR). The repair of damaged DNA is essential for cell survival, often requiring the DDR to attenuate other cellular processes such as the cell cycle, DNA replication, and transcription of genes not involved in DDR. The complex relationship between DDR and transcription has only recently been investigated. Transcription can facilitate the DDR in response to double-strand breaks (DSBs) and stimulate nucleotide excision repair (NER). However, transcription may need to be reduced to prevent potential interference with the repair machinery. In this review, we discuss various mechanisms that regulate transcription repression in response to different types of DNA damage, categorizing them by their range and duration of effect. Finally, we explore various models of transcription recovery following DNA damage-induced repression.

摘要

由DNA损伤导致的基因毒性应激通过一种称为DNA损伤反应(DDR)的信号级联反应得以解决。受损DNA的修复对于细胞存活至关重要,这通常需要DDR来减弱其他细胞过程,如细胞周期、DNA复制以及与DDR无关的基因转录。DDR与转录之间的复杂关系直到最近才得到研究。转录可以促进DDR对双链断裂(DSB)作出反应并刺激核苷酸切除修复(NER)。然而,可能需要降低转录以防止对修复机制产生潜在干扰。在本综述中,我们讨论了响应不同类型DNA损伤而调节转录抑制的各种机制,并根据其作用范围和持续时间对它们进行分类。最后,我们探讨了DNA损伤诱导的抑制后转录恢复的各种模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d94/11810087/c633fe776986/KTRN_A_2406717_F0001_OC.jpg

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