Kopasz, Anna Georgina and Mérey, Mihály and Vásárhelyi, Rebeka and Pek, Ramona and Imburchia, Victor and Henn, László and Kószó, Adrián Imre and Lakin, Nicholas D. and Ahel, Ivan and Huet, Sebastien and Czibula, Ágnes and Timinszky, Gyula (2026) Hyperosmotic stress induces PARP1-mediated HPF1-dependent mono(ADP-ribosyl)ation. FEBS LETTERS, 600. pp. 2800-2813. ISSN 0014-5793
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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.
| Item Type: | Article |
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| Additional Information: | Funding Agency and Grant Number: Cancer Research UK [C35050/A22284]; Agence Nationale de la Recherche [ANR-22-CE12-0039 AROSE]; Fondation pour la Recherche Mdicale [ECO202406019133]; Wellcome Trust [223107, 302632]; Biotechnology and Biological Sciences Research Council [BB/R007195/1, BB/W016613/1]; Nemzeti Kutatsi Fejlesztsi s Innovcis Hivatal [K143248, K151375] Funding text: We would like to thank the imaging support provided by the Cellular Imaging Laboratory (HUN-REN Biological Research Centre). This work was supported by the National Research Development and Innovation Office (K143248 and K151375 to G.T.). A.G.K. was supported by the University Research Scholarship Program (EKOP) funded by the Ministry for Innovation and Technology from the National Research, Development and Innovation Fund. The work in I.A.'s laboratory is supported by the Wellcome Trust (223107 and 302632); Biotechnology and Biological Sciences Research Council (BB/R007195/1 and BB/W016613/1) and Cancer Research United Kingdom (C35050/A22284). The work in S.H.'s laboratory was supported by the Agence Nationale de la Recherche (ANR-22-CE12-0039 AROSE). R.P. was supported by the Fondation pour la Recherche Medicale (ECO202406019133). The graphical abstract was created with BioRender.com. |
| Uncontrolled Keywords: | ACTIVATION; Biophysics; DNA breaks; poly(ADP-ribose); hyperosmotic stress; Checkpoint; ADP-RIBOSYLATION; Biochemistry & Molecular Biology; HPF1; CELLULAR-RESPONSE; MONO(ADP-RIBOSYL)ATION; |
| Subjects: | Q Science / természettudomány > Q1 Science (General) / természettudomány általában R Medicine / orvostudomány > R1 Medicine (General) / orvostudomány általában |
| SWORD Depositor: | MTMT SWORD |
| Depositing User: | MTMT SWORD |
| Date Deposited: | 22 Oct 2026 07:34 |
| Last Modified: | 22 Oct 2026 07:34 |
| URI: | https://real.mtak.hu/id/eprint/249082 |
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