Department of Biochemistry and Molecular Pharmacology, New York University Grossman School of Medicine, New York, NY 10016, USA; Howard Hughes Medical Institute, New York University Grossman School of Medicine, New York, NY 10016, USA.
Trends Biochem Sci. 2023 Oct;48(10):873-882. doi: 10.1016/j.tibs.2023.07.007. Epub 2023 Aug 7.
The nucleotide excision repair (NER) pathway removes helix-distorting lesions from DNA in all organisms. Escherichia coli has long been a model for understanding NER, which is traditionally divided into major and minor subpathways known as global genome repair (GGR) and transcription-coupled repair (TCR), respectively. TCR has been assumed to be mediated exclusively by Mfd, a DNA translocase of minimal NER phenotype. This review summarizes the evidence that shaped the traditional view of NER in bacteria, and reviews data supporting a new model in which GGR and TCR are inseparable. In this new model, RNA polymerase serves both as the essential primary sensor of bulky DNA lesions genome-wide and as the delivery platform for the assembly of functional NER complexes in living cells.
核苷酸切除修复（NER）途径可去除所有生物体 DNA 中的螺旋扭曲损伤。大肠杆菌一直是研究 NER 的模型，NER 传统上分为主要和次要途径，分别称为全基因组修复（GGR）和转录偶联修复（TCR）。TCR 被认为仅由 Mfd 介导，Mfd 是一种具有最小 NER 表型的 DNA 转位酶。本综述总结了形成细菌中传统 NER 观点的证据，并回顾了支持新模型的数据，该模型认为 GGR 和 TCR 是不可分割的。在这个新模型中，RNA 聚合酶既是广泛存在的大体积 DNA 损伤的必需初级传感器，也是功能性 NER 复合物在活细胞中组装的递呈平台。
