Nucleotide excision repair (NER) is a highly versatile and efficient DNA repair process, which is responsible for the removal of a large number of structurally diverse DNA lesions. Its extreme broad substrate specificity ranges from DNA damages formed upon exposure to ultraviolet radiation to numerous bulky DNA adducts induced by mutagenic environmental chemicals and cytotoxic drugs used in chemotherapy. Defective NER leads to serious diseases, such as xeroderma pigmentosum (XP). Eight XP complementation groups are known of which seven (XPA–XPG) are caused by mutations in genes involved in the NER process. The eighth gene, XPV, codes for the DNA polymerase ɳ, which replicates through DNA lesions in a process called translesion synthesis (TLS). Over the past decade, detailed structural information of these DNA repair proteins involved in eukaryotic NER and TLS have emerged. These structures allow us now to understand the molecular mechanism of the NER and TLS processes in quite some detail and we have begun to understand the broad substrate specificity of NER. In this review, we aim to highlight recent advances in the process of damage recognition and repair as well as damage tolerance by the XP proteins.

中文翻译：

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色素性干皮病 (XP) 蛋白的分子机制

核苷酸切除修复 (NER) 是一种高度通用和高效的 DNA 修复过程，负责去除大量结构多样的 DNA 损伤。其极其广泛的底物特异性范围从暴露于紫外线辐射时形成的 DNA 损伤到由诱变环境化学物质和化疗中使用的细胞毒性药物诱导的大量 DNA 加合物。有缺陷的 NER 会导致严重的疾病，例如色素性干皮病 (XP)。已知八个 XP 互补组，其中七个 (XPA-XPG) 是由参与 NER 过程的基因突变引起的。第八个基因 XPV 编码 DNA 聚合酶ɳ，它在称为跨病变合成 (TLS) 的过程中通过 DNA 病变进行复制。在过去的十年中，这些参与真核 NER 和 TLS 的 DNA 修复蛋白的详细结构信息已经出现。这些结构现在使我们能够相当详细地了解 NER 和 TLS 过程的分子机制，并且我们已经开始了解 NER 的广泛底物特异性。在这篇综述中，我们旨在强调 XP 蛋白在损伤识别和修复以及损伤耐受性过程中的最新进展。