Bryan Cameron, Cepeda Joel, Li Bingru, Yang Kun
Division of Chemical Biology and Medicinal Chemistry, College of Pharmacy, The University of Texas at Austin, Austin, Texas 78712, United States.
Chem Res Toxicol. 2025 Jun 16;38(6):997-1005. doi: 10.1021/acs.chemrestox.5c00125. Epub 2025 May 19.
Covalent DNA-protein cross-links (DPCs), if not resolved, can block DNA replication and transcription, resulting in genome instability. Compared to other types of DNA damage, how DPCs are formed and repaired is less understood. This review focuses on recent findings concerning DPCs derived from two types of abasic DNA lesions, apurinic/apyrimidinic sites and 3'-phospho-α,β-unsaturated aldehydes. It summarizes the newly reported DPCs and their identification by liquid chromatography tandem mass spectrometry. It also reviews the approaches for synthesizing stable and site-specific DPCs, and their applications for discovering the corresponding repair mechanisms. Finally, it discusses the future directions to better understand the mechanistic formation and repair of those DPCs.
共价DNA-蛋白质交联(DPCs)若不被修复,会阻断DNA复制和转录,导致基因组不稳定。与其他类型的DNA损伤相比,DPCs的形成和修复机制鲜为人知。本综述聚焦于源自两类无碱基DNA损伤(脱嘌呤/脱嘧啶位点和3'-磷酸-α,β-不饱和醛)的DPCs的最新研究结果。总结了新报道的DPCs及其通过液相色谱串联质谱法的鉴定方法。还综述了合成稳定且位点特异性DPCs的方法及其在发现相应修复机制中的应用。最后,讨论了为更好理解这些DPCs的形成和修复机制的未来研究方向。