Department of Chemistry and Hong Kong Branch of Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong.
Department of Chemical and Biological Engineering, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong.
Chem Res Toxicol. 2020 Nov 16;33(11):2739-2744. doi: 10.1021/acs.chemrestox.0c00289. Epub 2020 Oct 26.
The formation of covalently bound DNA-protein crosslinks (DPCs) is linked to the pathophysiology of cancers and many other degenerative diseases. Knowledge of the proteins that were frequently involved in forming DPCs will improve our understanding of the etiological mechanism of diseases and facilitate the establishment of preventive measures and treatment methods. By using SDS-PAGE and nano-LC coupled Orbitrap LC-MS/MS analyses, we identified, for the first time, that the major DNA-cross-linked proteins in HeLa cells exposed to a methylating agent (methylmethanesulfonate) or hydroxyl free radicals are transcription-associated proteins. In particular, histone H2B3B and poly(rC) binding protein 2 were identified as the most frequent DPC-forming proteins.
共价结合的 DNA-蛋白质交联（DPC）的形成与癌症和许多其他退行性疾病的病理生理学有关。了解经常参与形成 DPC 的蛋白质将有助于我们理解疾病的病因机制，并促进预防措施和治疗方法的建立。通过 SDS-PAGE 和纳米 LC 与轨道阱 LC-MS/MS 分析，我们首次鉴定出，暴露于甲基化剂（甲基甲磺酸酯）或羟基自由基的 HeLa 细胞中的主要 DNA 交联蛋白是与转录相关的蛋白。特别是，H2B3B 组蛋白和多（rC）结合蛋白 2 被鉴定为最频繁形成 DPC 的蛋白质。
