Characterization of DNA ADP-ribosyltransferase activities of PARP2 and PARP3: new insights into DNA ADP-ribosylation

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dc.contributor.authorZarkovic, Gabriella
dc.contributor.authorBelousova, Ekaterina
dc.contributor.authorTalhaoui, Ibtissam
dc.contributor.authorSaint-Pierre, Christine
dc.contributor.authorKutuzov, Mikhail M.
dc.contributor.authorMatkarimov, Bakhyt
dc.contributor.authorBiard, Denis
dc.contributor.authorGasparutto, Didier
dc.contributor.authorLavrik, Olga I.
dc.contributor.authorIshchenko, Alexander A.
dc.date.accessioned2020-03-26T05:32:04Z
dc.date.available2020-03-26T05:32:04Z
dc.date.issued2018-01
dc.descriptionhttps://academic.oup.com/nar/article/46/5/2417/4807332en_US
dc.description.abstractPoly(ADP-ribose) polymerases (PARPs) act as DNA break sensors and catalyze the synthesis of polymers of ADP-ribose (PAR) covalently attached to acceptor proteins at DNA damage sites. It has been demonstrated that both mammalian PARP1 and PARP2 PARylate double-strand break termini in DNA oligonucleotide duplexes in vitro. Here, we show that mammalian PARP2 and PARP3 can PARylate and mono(ADP-ribosyl)ate (MARylate), respectively, 5′- and 3′-terminal phosphate residues at double- and single-strand break termini of a DNA molecule containing multiple strand breaks. PARP3-catalyzed DNA MARylation can be considered a new type of reversible post-replicative DNA modification. According to DNA substrate specificity of PARP3 and PARP2, we propose a putative mechanistic model of PARP-catalyzed strand break–oriented ADP-ribosylation of DNA termini. Notably, PARP-mediated DNA ADP-ribosylation can be more effective than PARPs’ auto-ADP-ribosylation depending on the DNA substrates and reaction conditions used. Finally, we show an effective PARP3- or PARP2-catalyzed ADP-ribosylation of high-molecular-weight (∼3-kb) DNA molecules, PARP-mediated DNA PARylation in cell-free extracts and a persisting signal of anti-PAR antibodies in a serially purified genomic DNA from bleomycin-treated poly(ADP-ribose) glycohydrolase-depleted HeLa cells. These results suggest that certain types of complex DNA breaks can be effectively ADP-ribosylated by PARPs in cellular response to DNA damage.en_US
dc.identifier.citationZarkovic, G., Belousova, E. A., Talhaoui, I., Saint-Pierre, C., Kutuzov, M. M., Matkarimov, B. T., Biard, D., Gasparutto, D., Lavrik, O. I., & Ishchenko, A. A. (2018). Characterization of DNA ADP-ribosyltransferase activities of PARP2 and PARP3: new insights into DNA ADP-ribosylation. Nucleic Acids Research, 46(5), 2417–2431. https://doi.org/10.1093/nar/gkx1318en_US
dc.identifier.issn0305-1048
dc.identifier.other1362-4962
dc.identifier.other10.1093/nar/gkx1318
dc.identifier.urihttps://doi.org/10.1093/nar/gkx1318
dc.identifier.urihttp://nur.nu.edu.kz/handle/123456789/4544
dc.language.isoenen_US
dc.publisherOxford University Pressen_US
dc.relation.ispartofseriesNucleic Acids Research;Vol. 46, No. 5
dc.rightsAttribution-NonCommercial-ShareAlike 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/us/*
dc.subjectgenome integrityen_US
dc.subjectrepair and replicationen_US
dc.subjectPARP2en_US
dc.subjectPARP3en_US
dc.subjectResearch Subject Categories::MEDICINEen_US
dc.titleCharacterization of DNA ADP-ribosyltransferase activities of PARP2 and PARP3: new insights into DNA ADP-ribosylationen_US
dc.typeArticleen_US
workflow.import.sourcescience

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