Publicación:
Characterization of DNA ADP-ribosyltransferase activities of PARP2 and PARP3: New insights into DNA ADP-ribosylation
Characterization of DNA ADP-ribosyltransferase activities of PARP2 and PARP3: New insights into DNA ADP-ribosylation
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Fecha
2018
Autores
Zarkovic 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.
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Oxford University Press
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Abstracto
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. 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.
Descripción
Fondation ARC (http://www.arc-cancer.net) [PJA20151203415 to A.A.I.]; ERA.Net RUS Plus (www.eranet-rus.eu) [DNA PARYLATION #306 to A.A.I., RFBR-16–54-76010 to O.I.L.]; Ministry of Education and Science of the Republic of Kazakhstan [programs 0115RK02473 and 0115RK03029 to B.T.M.]; NU ORAU (http://www.nu.edu.kz) (to B.T.M.); RSF Grant [14–24-00038 to O.I.L.]; French National Research Agency ‘Labex program’ [ARCANE project ANR-11-LABX-0003–01 to C.S.-P., D.G.]; Fondation ARC Postdoctoral Fellowship (http://www.arc-cancer.net) [PDF20110603195 to I.T.]; CIENCIACTIVA/CONCYTEC Doctoral Fellowship (www.cienciactiva.gob.pe) (to G.Z.). Funding for open access charge: National Laboratory Astana, Nazarbayev University, Astana, Republic of Kazakhstan.
Palabras clave
unclassified drug,
bleomycin,
DNA,
genomic DNA,
glycosidase,
nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase,
nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase 2,
nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase 3,
poly(adenosine diphosphate ribose),
Article,
cell free system,
controlled study,
DNA damage,
DNA modification,
DNA replication,
double stranded DNA break,
enzyme active site,
enzyme activity,
enzyme mechanism,
enzyme specificity,
HeLa cell line,
human,
human cell,
molecular weight,
mono adenosine diphosphate ribosylation,
priority journal,
single stranded DNA break