Hyperosmotic stress induces PARP1-mediated HPF1-dependent mono(ADP-ribosyl)ation.

IF 3 4区 生物学 Q1 Biochemistry, Genetics and Molecular Biology
Anna Georgina Kopasz, Mihály Mérey, Rebeka Vásárhelyi, Ramóna Pék, Victor Imburchia, László Henn, Adrián Kószó, Nicholas D Lakin, Ivan Ahel, Sébastien Huet, Ágnes Czibula, Gyula Timinszky
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引用次数: 0

Abstract

While the downstream effectors of the hyperosmotic stress response are relatively well characterized, the primary molecular sensors responsible for initial stress detection remain poorly defined. In this study, we demonstrate that hyperosmotic stress triggers a rapid and transient mono(ADP-ribosyl)ation (MARylation). Beside MARylation, signs of acute genotoxicity are missing and CHK1 activation is observed only upon recovery from osmotic stress. Our data indicate that PARP1 catalyzes its own MARylation in an HPF1 co-factor dependent manner. Biochemical assays further demonstrate that the mono-ADP-ribose moiety is resistant to hydroxylamine treatment, which is a feature of HPF1-directed O-glycosidic bonds. Together, these findings support a model in which PARP1 acts as a sensor of chromatin structure changes induced by hyperosmotic stress leading to its autoMARylation.

高渗应激诱导parp1介导的hpf1依赖性单核苷酸(adp -核糖基)化。
虽然高渗应激反应的下游效应物已相对较好地表征,但负责初始应激检测的主要分子传感器仍然定义不清。在这项研究中,我们证明了高渗应激触发快速和短暂的单(adp -核糖基)化(MARylation)。除了MARylation,急性遗传毒性的迹象是缺失的,CHK1激活仅在从渗透胁迫中恢复时观察到。我们的数据表明PARP1以HPF1辅助因子依赖的方式催化其自身的MARylation。生化分析进一步表明,单adp核糖部分对羟胺处理具有抗性,这是hpf1导向的o-糖苷键的特征。总之,这些发现支持一个模型,其中PARP1作为高渗胁迫诱导的染色质结构变化的传感器,导致其自动arylation。
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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来源期刊
FEBS Letters
FEBS Letters 生物-生化与分子生物学
CiteScore
7.00
自引率
2.90%
发文量
303
审稿时长
1.0 months
期刊介绍: FEBS Letters is one of the world''s leading journals in molecular biology and is renowned both for its quality of content and speed of production. Bringing together the most important developments in the molecular biosciences, FEBS Letters provides an international forum for Minireviews, Research Letters and Hypotheses that merit urgent publication.
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