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