Department of Molecular and Cellular Biology, University of Geneva, Geneva 4 1211, Switzerland.
Department of Molecular and Cellular Biology, University of Geneva, Geneva 4 1211, Switzerland.
DNA Repair (Amst). 2024 Jul;139:103691. doi: 10.1016/j.dnarep.2024.103691. Epub 2024 May 9.
The ATP-dependent molecular chaperone Cdc48 (in yeast) and its human counterpart p97 (also known as VCP), are essential for a variety of cellular processes, including the removal of DNA-protein crosslinks (DPCs) from the DNA. Growing evidence demonstrates in the last years that Cdc48/p97 is pivotal in targeting ubiquitinated and SUMOylated substrates on chromatin, thereby supporting the DNA damage response. Along with its cofactors, notably Ufd1-Npl4, Cdc48/p97 has emerged as a central player in the unfolding and processing of DPCs. This review introduces the detailed structure, mechanism and cellular functions of Cdc48/p97 with an emphasis on the current knowledge of DNA-protein crosslink repair pathways across several organisms. The review concludes by discussing the potential therapeutic relevance of targeting p97 in DPC repair.
ATP 依赖的分子伴侣 Cdc48（在酵母中）及其人类同源物 p97（也称为 VCP）对于多种细胞过程是必不可少的，包括从 DNA 上去除 DNA-蛋白交联（DPCs）。近年来越来越多的证据表明，Cdc48/p97 在靶向染色质上泛素化和 SUMO 化的底物方面起着关键作用，从而支持 DNA 损伤反应。Cdc48/p97 与其辅助因子（尤其是 Ufd1-Npl4）一起，已成为 DPC 展开和加工的核心参与者。这篇综述介绍了 Cdc48/p97 的详细结构、机制和细胞功能，重点介绍了几种生物体中 DNA-蛋白交联修复途径的最新知识。该综述最后讨论了靶向 p97 进行 DPC 修复的潜在治疗相关性。
