Skip to Main content Skip to Navigation
Journal articles

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

Abstract : Poly(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. PARP3catalyzed 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, PARPmediated 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 PARP2catalyzed 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.
Complete list of metadata

https://hal.archives-ouvertes.fr/hal-03423702
Contributor : Ibtissam TALHAOUI Connect in order to contact the contributor
Submitted on : Wednesday, November 10, 2021 - 11:02:15 AM
Last modification on : Saturday, June 25, 2022 - 10:52:45 PM
Long-term archiving on: : Friday, February 11, 2022 - 6:25:40 PM

File

Characterization of DNA ADP-ri...
Publisher files allowed on an open archive

Licence


Distributed under a Creative Commons Attribution - NonCommercial 4.0 International License

Identifiers

Citation

Gabriella Zarkovic, Ekaterina A Belousova, Ibtissam Talhaoui, Christine Saint-Pierre, Mikhail M Kutuzov, et al.. Characterization of DNA ADP-ribosyltransferase activities of PARP2 and PARP3: new insights into DNA ADP-ribosylation. Nucleic Acids Research, Oxford University Press, 2018, 46 (5), pp.2417 - 2431. ⟨10.1093/nar/gkx1318⟩. ⟨hal-03423702⟩

Share

Metrics

Record views

103

Files downloads

8