Ultraviolet (UV) irradiation and other genotoxic stresses induce bulky DNA lesions, which threaten genome stability and cell viability. Cells have evolved two main repair pathways to remove such lesions: global genome nucleotide excision repair (GG-NER) and transcription-coupled nucleotide excision repair (TC-NER). The modes by which these subpathways recognize DNA lesions are distinct, but they converge onto the same downstream steps for DNA repair. Here, we first summarize the current understanding of these repair mechanisms, specifically focusing on the roles of stalled RNA polymerase II, Cockayne syndrome protein B (CSB), CSA and UV-stimulated scaffold protein A (UVSSA) in TC-NER. We also discuss the intriguing role of protein ubiquitylation in this process. Additionally, we highlight key aspects of the effect of UV irradiation on transcription and describe the role of signaling cascades in orchestrating this response. Finally, we describe the pathogenic mechanisms underlying xeroderma pigmentosum and Cockayne syndrome, the two main diseases linked to mutations in NER factors.

中文翻译：

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转录偶联的核苷酸切除修复和对紫外线诱导的 DNA 损伤的转录反应

紫外线 (UV) 照射和其他基因毒性应激会导致大量 DNA 损伤，从而威胁基因组稳定性和细胞活力。细胞已经进化出两种主要的修复途径来消除此类损伤：全局基因组核苷酸切除修复（GG-NER）和转录偶联核苷酸切除修复（TC-NER）。这些子通路识别 DNA 损伤的模式是不同的，但它们汇聚到相同的 DNA 修复下游步骤。在这里，我们首先总结了目前对这些修复机制的理解，特别关注停滞的RNA聚合酶II、科凯恩综合征蛋白B（CSB）、CSA和紫外线刺激的支架蛋白A（UVSSA）在TC-NER中的作用。我们还讨论了蛋白质泛素化在此过程中的有趣作用。此外，我们强调了紫外线照射对转录影响的关键方面，并描述了信号级联在协调这种反应中的作用。最后，我们描述了着色性干皮病和科凯恩综合征的致病机制，这两种主要疾病与 NER 因子突变有关。