Insight into DNA substrate specificity of PARP1-catalysed DNA poly(ADP-ribosyl)ation
| العنوان: | Insight into DNA substrate specificity of PARP1-catalysed DNA poly(ADP-ribosyl)ation |
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| المؤلفون: | Alexander A. Ishchenko, Bakhyt T. Matkarimov, Assel Kiribayeva, Bekbolat Khassenov, Elie Matta |
| المساهمون: | Réparation de l’ADN (CNRS UMR 8200), Stabilité Génétique et Oncogenèse (UMR 8200), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS) |
| المصدر: | Scientific Reports, Vol 10, Iss 1, Pp 1-11 (2020) Scientific Reports Scientific Reports, Nature Publishing Group, 2020, 10 (1), ⟨10.1038/s41598-020-60631-0⟩ |
| بيانات النشر: | Nature Publishing Group, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, DNA damage, Poly (ADP-Ribose) Polymerase-1, lcsh:Medicine, Catalysis, Article, law.invention, Substrate Specificity, 03 medical and health sciences, chemistry.chemical_compound, Residue (chemistry), PARP1, law, Transferases, DNA-binding proteins, Animals, Humans, lcsh:Science, Polymerase, Multidisciplinary, 030102 biochemistry & molecular biology, biology, lcsh:R, Substrate (chemistry), [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, DNA, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], 030104 developmental biology, Monomer, chemistry, DNA repair enzymes, Enzyme mechanisms, Biophysics, biology.protein, Recombinant DNA, Cattle, lcsh:Q |
| الوصف: | DNA-dependent poly(ADP-ribose) polymerases (PARPs) PARP1, PARP2 and PARP3 act as DNA break sensors signalling DNA damage. Upon detecting DNA damage, these PARPs use nicotine adenine dinucleotide as a substrate to synthesise a monomer or polymer of ADP-ribose (MAR or PAR, respectively) covalently attached to the acceptor residue of target proteins. Recently, it was demonstrated that PARP1–3 proteins can directly ADP-ribosylate DNA breaks by attaching MAR and PAR moieties to terminal phosphates. Nevertheless, little is still known about the mechanisms governing substrate recognition and specificity of PARP1, which accounts for most of cellular PARylation activity. Here, we characterised PARP1-mediated DNA PARylation of DNA duplexes containing various types of breaks at different positions. The 3′-terminal phosphate residue at double-strand DNA break ends served as a major acceptor site for PARP1-catalysed PARylation depending on the orientation and distance between DNA strand breaks in a single DNA molecule. A preference for ADP-ribosylation of DNA molecules containing 3′-terminal phosphate over PARP1 auto-ADP-ribosylation was observed, and a model of DNA modification by PARP1 was proposed. Similar results were obtained with purified recombinant PARP1 and HeLa cell-free extracts. Thus, the biological effects of PARP-mediated ADP-ribosylation may strongly depend on the configuration of complex DNA strand breaks. |
| اللغة: | English |
| تدمد: | 2045-2322 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::aee9c9bb1a6b1d20e79e8ab4af91bb54Test http://link.springer.com/article/10.1038/s41598-020-60631-0Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....aee9c9bb1a6b1d20e79e8ab4af91bb54 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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