Costa Renata M A, Chiganças Vanessa, Galhardo Rodrigo da Silva, Carvalho Helotonio, Menck Carlos F M
Departamento de Microbiologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Av. Prof. Lineu Prestes, 1374 Ed. Biomédicas 2, Sao Paulo 05508-900, SP, Brazil.
Biochimie. 2003 Nov;85(11):1083-99. doi: 10.1016/j.biochi.2003.10.017.
Nucleotide excision repair (NER) is the most versatile mechanism of DNA repair, recognizing and dealing with a variety of helix-distorting lesions, such as the UV-induced photoproducts cyclobutane pyrimidine dimers (CPDs) and pyrimidine 6-4 pyrimidone photoproducts (6-4 PPs). In this review, we describe the main protein players and the different sequential steps of the eukaryotic NER mechanism in human cells, from lesion recognition to damage removal and DNA synthesis. Studies on the dynamics of protein access to the damaged site, and the kinetics of lesion removal contribute to the knowledge of how the cells respond to genetic insult. DNA lesions as well as NER factors themselves are also implicated in changes in cell metabolism, influencing cell cycle progression or arrest, apoptosis and genetic instability. These changes are related to increased mutagenesis and carcinogenesis. Finally, the recent collection of genomic data allows one to recognize the high conservation and the evolution of eukaryotic NER. The distribution of NER orthologues in different organisms, from archaea to the metazoa, displays challenging observations. Some of NER proteins are widespread in nature, probably representing ancient DNA repair proteins, which are candidates to participate in a primitive NER mechanism.
核苷酸切除修复（NER）是DNA修复中最通用的机制，可识别并处理多种扭曲螺旋的损伤，如紫外线诱导的光产物环丁烷嘧啶二聚体（CPD）和嘧啶6-4嘧啶酮光产物（6-4PP）。在本综述中，我们描述了人类细胞中真核生物NER机制的主要蛋白质成分以及从损伤识别到损伤去除和DNA合成的不同连续步骤。对蛋白质到达损伤位点的动力学以及损伤去除动力学的研究有助于了解细胞如何应对基因损伤。DNA损伤以及NER因子本身也与细胞代谢变化有关，影响细胞周期进程或停滞、细胞凋亡和基因不稳定。这些变化与诱变和致癌作用的增加有关。最后，最近收集的基因组数据使人们能够认识到真核生物NER的高度保守性和进化。从古细菌到后生动物，不同生物体中NER直系同源物的分布呈现出具有挑战性的观察结果。一些NER蛋白在自然界广泛存在，可能代表古老的DNA修复蛋白，它们是参与原始NER机制的候选者。
