Hyperosmotic stress induces <scp>PARP1</scp> ‐mediated <scp>HPF1</scp> ‐dependent mono( <scp>ADP</scp> ‐ribosyl)ation

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.

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Publication Details

Journal
FEBS Letters
Published
2026-03-31
DOI
https://doi.org/10.1002/1873-3468.70334
Primary Topic
PARP inhibition in cancer therapy
Type
article
Field-Weighted Citation Impact
0.00

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article

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

Nicholas D. Lakin, Ágnes Czibula, S. Huet, Gyula Timinszky et al.
FEBS Letters
PARP inhibition in cancer therapy
article

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

Nicholas D. Lakin, Ágnes Czibula, S. Huet, Gyula Timinszky, Anna Georgina Kopasz, László Henn, Mihály Mérey, Victor Imburchia, Ramóna Pék, Rebeka Vásárhelyi, Adrián Kószó, Ivan Ahel
article en

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.

FEBS Letters
Centre National de la Recherche Scientifique (FR), University of Szeged (HU), HUN-REN Szegedi Biológiai Kutatóközpont (HU), University of Oxford (GB), Institut de génétique et de développement de Rennes (FR), Université de Rennes (FR)
Wellcome Trust, Cancer Research UK, Agence Nationale de la Recherche, Fondation pour la Recherche Médicale, Nemzeti Kutatási Fejlesztési és Innovációs Hivatal, Biotechnology and Biological Sciences Research Council
Openalex Percentile: Top 41%
PARP inhibition in cancer therapy
DOIOpen Access PDFOpenAlex
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