Park Chin-Ju, Choi Byong-Seok
Department of Chemistry, National Creative Initiative Center, Korea Advanced Institute of Science and Technology, Guseong-dong, Yuseong-gu, Daejon.
FEBS J. 2006 Apr;273(8):1600-8. doi: 10.1111/j.1742-4658.2006.05189.x.
Xeroderma pigmentosum (XP) is an inherited disease in which cells from patients exhibit defects in nucleotide excision repair (NER). XP proteins A-G are crucial in the processes of DNA damage recognition and incision, and patients with XP can carry mutations in any of the genes that specify these proteins. In mammalian cells, NER is a dynamic process in which a variety of proteins interact with one another, via modular domains, to carry out their functions. XP proteins are key players in several steps of the NER process, including DNA strand discrimination (XPA, in complex with replication protein A), repair complex formation (XPC, in complex with hHR23B; XPF, in complex with ERCC1) and repair factor recruitment (transcription factor IIH, in complex with XPG). Through these protein-protein interactions, various types of bulky DNA adducts can be recognized and repaired. Communication between the NER system and other cellular pathways is also achieved by selected binding of the various structural domains. Here, we summarize recent studies on the domain structures of human NER components and the regulatory networks that utilize these proteins. Data provided by these studies have helped to illuminate the complex molecular interactions among NER factors in the context of DNA repair.
着色性干皮病（XP）是一种遗传性疾病，患者的细胞在核苷酸切除修复（NER）方面存在缺陷。XP蛋白A - G在DNA损伤识别和切割过程中至关重要，XP患者可能在指定这些蛋白的任何基因中携带突变。在哺乳动物细胞中，NER是一个动态过程，多种蛋白质通过模块化结构域相互作用以执行其功能。XP蛋白是NER过程几个步骤中的关键参与者，包括DNA链识别（XPA与复制蛋白A形成复合物）、修复复合物形成（XPC与hHR23B形成复合物；XPF与ERCC1形成复合物）以及修复因子募集（转录因子IIH与XPG形成复合物）。通过这些蛋白质 - 蛋白质相互作用，可以识别和修复各种类型的大体积DNA加合物。NER系统与其他细胞途径之间的通信也通过各种结构域的选择性结合来实现。在此，我们总结了关于人类NER成分的结构域结构以及利用这些蛋白质的调控网络的最新研究。这些研究提供的数据有助于阐明DNA修复背景下NER因子之间复杂的分子相互作用。
