Cdc48/p97 分离酶：聚焦 DNA 蛋白交联

IF 3 3区生物学 Q2 GENETICS & HEREDITY

DNA Repair Pub Date : 2024-05-09 DOI:10.1016/j.dnarep.2024.103691

Audrey Noireterre, Françoise Stutz

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引用次数: 0

摘要

依赖 ATP 的分子伴侣 Cdc48（在酵母中）及其人类对应物 p97（又称 VCP）对多种细胞过程都至关重要，其中包括 DNA 上 DNA 蛋白交联（DPC）的清除。近年来，越来越多的证据表明，Cdc48/p97 在靶向染色质上的泛素化和 SUMOylated 底物，从而支持 DNA 损伤反应方面起着关键作用。Cdc48/p97 与其辅助因子，特别是 Ufd1-Npl4，已成为 DPCs 展开和处理过程中的核心角色。这篇综述介绍了 Cdc48/p97 的详细结构、机制和细胞功能，重点是目前对几种生物的 DNA 蛋白交联修复途径的了解。综述最后讨论了在 DPC 修复中靶向 p97 的潜在治疗意义。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Cdc48/p97 segregase: Spotlight on DNA-protein crosslinks

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.

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来源期刊

DNA Repair 生物-毒理学

CiteScore

7.60

自引率

5.30%

发文量

审稿时长

59 days

期刊介绍： DNA Repair provides a forum for the comprehensive coverage of DNA repair and cellular responses to DNA damage. The journal publishes original observations on genetic, cellular, biochemical, structural and molecular aspects of DNA repair, mutagenesis, cell cycle regulation, apoptosis and other biological responses in cells exposed to genomic insult, as well as their relationship to human disease. DNA Repair publishes full-length research articles, brief reports on research, and reviews. The journal welcomes articles describing databases, methods and new technologies supporting research on DNA repair and responses to DNA damage. Letters to the Editor, hot topics and classics in DNA repair, historical reflections, book reviews and meeting reports also will be considered for publication.