National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; School of Medicine, Sun Yat-Sen University, Guangzhou 510275, China.
School of Life Science and Engineering, Foshan University, Guangdong, China.
DNA Repair (Amst). 2019 May;77:1-9. doi: 10.1016/j.dnarep.2019.02.012. Epub 2019 Feb 22.
Nucleotide excision repair (NER) is a versatile system that deals with various bulky and helix-distorting DNA lesions caused by UV and environmental mutagens. Based on how lesion recognition occurs, NER has been separated into global genome repair (GGR) and transcription-coupled repair (TCR). The yeast Rad7-Rad16 complex is indispensable for the GGR sub-pathway. Rad7-Rad16 binds to UV-damaged DNA in a synergistic fashion with Rad4, the main lesion recognizer, to achieve efficient recognition of lesions. In addition, Rad7-Rad16 associates with Elc1 and Cul3 to form an EloC-Cul-SOCS-box (ECS)-type E3 ubiquitin ligase complex that ubiquitinates Rad4 in response to UV radiation. However, the structure and architecture of the Rad7-Rad16-Elc1-Cul3 complex remain unsolved. Here, we determined the structure of the Rad7-Elc1 complex and revealed key interaction regions responsible for the formation of the Rad7-Rad16-Elc1-Cul3 complex. These results provide new insights into the assembly of the Rad7-Rad16-Elc1-Cul3 complex and structural framework for further studies.
核苷酸切除修复（NER）是一种多功能系统，可处理由 UV 和环境诱变剂引起的各种大体积和螺旋扭曲的 DNA 损伤。根据损伤识别如何发生，NER 已分为全基因组修复（GGR）和转录偶联修复（TCR）。酵母 Rad7-Rad16 复合物对于 GGR 亚途径是必不可少的。Rad7-Rad16 与主要损伤识别器 Rad4 以协同方式结合到 UV 损伤的 DNA 上，以实现对损伤的有效识别。此外，Rad7-Rad16 与 Elc1 和 Cul3 结合形成 EloC-Cul-SOCS 盒（ECS）型 E3 泛素连接酶复合物，该复合物响应 UV 辐射泛素化 Rad4。然而，Rad7-Rad16-Elc1-Cul3 复合物的结构和架构仍然未解决。在这里，我们确定了 Rad7-Elc1 复合物的结构，并揭示了负责形成 Rad7-Rad16-Elc1-Cul3 复合物的关键相互作用区域。这些结果为 Rad7-Rad16-Elc1-Cul3 复合物的组装提供了新的见解，并为进一步研究提供了结构框架。
