Sugasawa Kaoru
Cellular Physiology Laboratory, RIKEN Discovery Research Institute, Hirosawa, Wako, Saitama, Japan.
Methods Enzymol. 2006;408:171-88. doi: 10.1016/S0076-6879(06)08011-6.
In mammalian nucleotide excision repair (NER) operating throughout the genome, DNA lesions are recognized by protein factors that specifically bind to the damaged sites. Such damage recognition factors involve the xeroderma pigmentosum group C (XPC) protein complex and ultraviolet (UV)-damaged DNA-binding protein (UV-DDB). To assess specific DNA-binding activities of these factors, it is useful to take advantage of biochemical assays using DNA substrates that contain a defined lesion and/or artificial structure in a site-specific manner. In addition, it has been shown that both XPC and UV-DDB are ubiquitylated in response to UV irradiation of cells. This ubiquitylation is mediated by ubiquitin ligase associated with UV-DDB and is important for the NER process of UV-induced lesions. Methods for detecting the UV-DDB-dependent ubiquitylation in vivo and in vitro are also described.
在整个基因组中发挥作用的哺乳动物核苷酸切除修复(NER)过程中,DNA损伤由特异性结合损伤位点的蛋白质因子识别。此类损伤识别因子包括着色性干皮病C组(XPC)蛋白复合物和紫外线(UV)损伤DNA结合蛋白(UV-DDB)。为了评估这些因子的特异性DNA结合活性,利用生化分析方法是很有用的,该方法使用以位点特异性方式包含特定损伤和/或人工结构的DNA底物。此外,研究表明,细胞经紫外线照射后,XPC和UV-DDB都会发生泛素化。这种泛素化由与UV-DDB相关的泛素连接酶介导,对紫外线诱导损伤的NER过程很重要。本文还描述了体内和体外检测UV-DDB依赖性泛素化的方法。