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核苷酸切除修复与基因表达的偶联。

Coupling between nucleotide excision repair and gene expression.

机构信息

a Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE-UBA-CONICET) and Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales , Universidad de Buenos Aires, Ciudad Universitaria , Buenos Aires , Argentina.

b Fondazione Istituto FIRC di Oncologia Molecolare (IFOM) , Milan , Italy.

出版信息

RNA Biol. 2018;15(7):845-848. doi: 10.1080/15476286.2018.1464354. Epub 2018 May 17.

DOI:10.1080/15476286.2018.1464354
PMID:29683386
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6161737/
Abstract

Gene expression and DNA repair are fundamental processes for life. During the last decade, accumulating experimental evidence point towards different modes of coupling between these processes. Here we discuss the molecular mechanisms by which RNAPII-dependent transcription affects repair by the Nucleotide Excision Repair system (NER) and how NER activity, through the generation of single stranded DNA intermediates and activation of the DNA damage response kinase ATR, drives gene expression in a genotoxic scenario. Since NER-dependent repair is compromised in Xeroderma Pigmentosum (XP) patients, and having in mind that these patients present a high degree of clinical heterogeneity, we speculate that some of the clinical features of XP patients can be explained by misregulation of gene expression.

摘要

基因表达和 DNA 修复是生命的基本过程。在过去的十年中，越来越多的实验证据表明这两个过程之间存在不同的耦合模式。在这里，我们讨论了 RNA 聚合酶 II 依赖性转录如何影响核苷酸切除修复系统 (NER) 的修复，以及 NER 活性如何通过产生单链 DNA 中间体和激活 DNA 损伤反应激酶 ATR 来驱动基因表达在遗传毒性情况下。由于 Xeroderma Pigmentosum (XP) 患者的 NER 依赖性修复受损，并且考虑到这些患者表现出高度的临床异质性，我们推测 XP 患者的一些临床特征可以通过基因表达的失调来解释。

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ATR Plays a Direct Antiapoptotic Role at Mitochondria, which Is Regulated by Prolyl Isomerase Pin1.ATR在线粒体中发挥直接的抗凋亡作用，该作用由脯氨酰异构酶Pin1调控。
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UVB induces a genome-wide acting negative regulatory mechanism that operates at the level of transcription initiation in human cells.紫外线B（UVB）在人类细胞中诱导一种全基因组作用的负调控机制，该机制在转录起始水平发挥作用。
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