SUMO4促进DNA双链断裂修复所需的SUMO解偶联

IF 14.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Cell Pub Date : 2025-03-06 DOI:10.1016/j.molcel.2025.02.004

Alexander J. Garvin, Alexander J. Lanz, George E. Ronson, Matthew J.W. Mackintosh, Katarzyna Starowicz, Alexandra K. Walker, Yara Aghabi, Hannah MacKay, Ruth M. Densham, Jai S. Bhachoo, Aneika C. Leney, Joanna R. Morris

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引用次数: 0

摘要

通过泛素和小泛素样修饰物SUMO1-3的小修饰蛋白信号传导的振幅对于DNA修复蛋白积累、活性和清除的正确阶段以及哺乳动物DNA双链断裂（DSB）修复的完成至关重要。然而，如何在反应中描述sumo共轭信号是知之甚少的。与此同时，非偶联的SUMO蛋白SUMO4的作用仍然是个谜。在这里，我们发现人类需要SUMO4来防止dna损伤诱导的过度SUMOylation和RAP80的有害过度积累。在机理上，我们发现SUMO4独立于其偶联作用并增强了SENP1的催化活性。这些数据表明SUMO4是SUMO解偶联成分，并表明SUMO4:SENP1是dna损伤诱导的SUMO信号传导的关键调节因子。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

SUMO4 promotes SUMO deconjugation required for DNA double-strand-break repair

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SUMO4 promotes SUMO deconjugation required for DNA double-strand-break repair

The amplitudes of small-modifier protein signaling through ubiquitin and the small ubiquitin-like modifiers, SUMO1–3, are critical to the correct phasing of DNA repair protein accumulation, activity, and clearance and for the completion of mammalian DNA double-strand-break (DSB) repair. However, how SUMO-conjugate signaling in the response is delineated is poorly understood. At the same time, the role of the non-conjugated SUMO protein, SUMO4, has remained enigmatic. Here, we reveal that human SUMO4 is required to prevent excessive DNA-damage-induced SUMOylation and deleterious over-accumulation of RAP80. Mechanistically we show that SUMO4 acts independently of its conjugation and potentiates SENP1 catalytic activity. These data identify SUMO4 as a SUMO deconjugation component and show that SUMO4:SENP1 are critical regulators of DNA-damage-induced SUMO signaling.

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来源期刊

Molecular Cell 生物-生化与分子生物学

CiteScore

26.00

自引率

3.80%

发文量

389

审稿时长

1 months

期刊介绍： Molecular Cell is a companion to Cell, the leading journal of biology and the highest-impact journal in the world. Launched in December 1997 and published monthly. Molecular Cell is dedicated to publishing cutting-edge research in molecular biology, focusing on fundamental cellular processes. The journal encompasses a wide range of topics, including DNA replication, recombination, and repair; Chromatin biology and genome organization; Transcription; RNA processing and decay; Non-coding RNA function; Translation; Protein folding, modification, and quality control; Signal transduction pathways; Cell cycle and checkpoints; Cell death; Autophagy; Metabolism.