核苷酸切除修复对UVB光损伤的识别机制

Recognition Mechanism of Nucleotide Excision Repair to UVB-induced Photodamages

中波紫外线(UVB)会对皮肤造成各种损伤,这些都根源于UVB对皮肤细胞DNA的光损伤。光损伤产物主要有环丁烷嘧啶二聚体(CPD)和6-4光产物(6-4PP)两类,还包括少量的氧化损伤。CPD和6-4PP的修复是由核苷酸切除修复(NER)执行的。NER可分为全基因组核苷酸切除修复(GGR)和转录耦联核苷酸切除修复(TCR)两个亚途径。识别因子XPC通过一种不直接识别损伤本身的机制在GGR识别过程中发挥作用;在TCR识别过程中强调了关键因子CSB单体及二聚体两种形式的转换。在染色质水平上,DDB介导的泛素化作用是NER识别过程中重要的调控要素。另外,完成使命的识别因子的最终走向也是NER途径中的一个重要环节。通过分析上述生化过程,较清楚地总结了GGR及TCR对UVB导致的光损伤的识别机制。

The skin injury caused by ultraviolet B （UVB） can trace back to the UVB-induced DNA photodamages. Cyclobutyl pyrimidine dimers （CPDs） , （6--4） photoproducts （6-4PPs） and some oxidative damages constitute the most important photodamages. Nucleotide excision repair （NER） is involved in the removal of CPDs and 6-4PPs. NER is composed of global genome nucleotide excision repair （GGR） and transcription-coupled nucleotide excision＂ repair （TCR）. The recognition mechanisms of GGR and TCR to UVB-induced photodamages were summarized： Xeroderma Pigmentosum group C （ XPC）, the recognition factor in GGR, executed its function avoiding direct contacting with lesions; the conversion between monomer and dimer of cockayne syndrome B protein （CSB） was underlined in the recognition of TCR; ubiquitylation mediated by DNA damage binding protein （DDB） played an important role in NER recognization at chromatin level; moreover, the fate of the recognition factors （XPC, RNAPIIo） was also discussed.