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
{"title":"Hyperosmotic stress induces PARP1-mediated HPF1-dependent mono(ADP-ribosyl)ation.","authors":"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","doi":"10.1002/1873-3468.70334","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.0000,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"FEBS Letters","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1002/1873-3468.70334","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Biochemistry, Genetics and Molecular Biology","Score":null,"Total":0}
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.
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.