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

  • FEBS Lett. 2026 Mar 31. doi: 10.1002/1873-3468.70334.
Anna Georgina Kopasz  1  2 ,  Mihály Mérey  1  2 ,  Rebeka Vásárhelyi  1  3 ,  Ramóna Pék  4 ,  Victor Imburchia  4 ,  László Henn  1 ,  Adrián Kószó  1 ,  Nicholas D Lakin  5 ,  Ivan Ahel  6 ,  Sébastien Huet  4 ,  Ágnes Czibula  1  7 ,  Gyula Timinszky  1
Affiliations
  • 1. Laboratory of DNA Damage and Nuclear Dynamics, Institute of Genetics, HUN-REN Biological Research Centre, Szeged, Hungary.
  • 2. Doctoral School of Multidisciplinary Medical Sciences, University of Szeged, Hungary.
  • 3. Doctoral School of Biology, Faculty of Science and Informatics, University of Szeged, Hungary.
  • 4. Univ Rennes, CNRS, IGDR (Institut de Génétique et Développement de Rennes) - UMR 6290, BIOSIT (Biologie, Santé, Innovation Technologique de Rennes) - UMS 3480, France.
  • 5. Department of Biochemistry, University of Oxford, UK.
  • 6. Sir William Dunn School of Pathology, University of Oxford, UK.
  • 7. Department of Immunology, Albert Szent-Györgyi Medical School, University of Szeged, Hungary.
PMID: 41914023 DOI: 10.1002/1873-3468.70334
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.

Keywords
HPF1; PARP1; hyperosmotic stress; mono(ADP‐ribosyl)ation.
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