Doctor of Philosophy Program in Biochemistry (International Program), Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
Int J Mol Sci. 2021 Jan 19;22(2):952. doi: 10.3390/ijms22020952.
Double stranded DNA (dsDNA), the repository of genetic information in bacteria, archaea and eukaryotes, exhibits a surprising instability in the intracellular environment; this fragility is exacerbated by exogenous agents, such as ultraviolet radiation. To protect themselves against the severe consequences of DNA damage, cells have evolved at least six distinct DNA repair pathways. Here, we review recent key findings of studies aimed at understanding one of these pathways: bacterial nucleotide excision repair (NER). This pathway operates in two modes: a global genome repair (GGR) pathway and a pathway that closely interfaces with transcription by RNA polymerase called transcription-coupled repair (TCR). Below, we discuss the architecture of key proteins in bacterial NER and recent biochemical, structural and single-molecule studies that shed light on the lesion recognition steps of both the GGR and the TCR sub-pathways. Although a great deal has been learned about both of these sub-pathways, several important questions, including damage discrimination, roles of ATP and the orchestration of protein binding and conformation switching, remain to be addressed.
双链 DNA（dsDNA）是细菌、古菌和真核生物中遗传信息的储存库，其在细胞内环境中表现出惊人的不稳定性；这种脆弱性会因紫外线等外源因素而加剧。为了防止 DNA 损伤带来的严重后果，细胞已经进化出至少六种不同的 DNA 修复途径。在这里，我们回顾了旨在理解其中一种途径（细菌核苷酸切除修复（NER））的研究的最新关键发现。该途径以两种模式运作：一种是全基因组修复（GGR）途径，另一种是与 RNA 聚合酶转录密切相关的途径，称为转录偶联修复（TCR）。下面，我们将讨论细菌 NER 中关键蛋白的结构以及最近的生化、结构和单分子研究，这些研究揭示了 GGR 和 TCR 亚途径中损伤识别步骤。尽管已经对这两个亚途径有了很多了解，但仍有几个重要问题有待解决，包括损伤识别、ATP 的作用以及蛋白质结合和构象转换的协调。
