Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Adenosine diphosphate (ADP)-ribosylation is a chemical modification of macromolecules that plays an important role in regulation of quintessential biological processes such as DNA repair, transcription, chromatin remodelling, stress response, apoptosis, bacterial metabolism and many others. ADP-ribosylation is carried out by ADP-ribosyltransferase proteins, such as poly (ADP-ribose) polymerases (PARPs) that transfer either monomer or polymers of ADP-ribose onto the molecular targets by using nicotinamide adenine dinucleotide (NAD+ ) as a cofactor. Traditionally, proteins have been described as primary targets of ADP-ribosylation; however, there has been growing evidence that DNA may be a common target as well. Here, we show using biochemical studies that PARP3, a DNA damage-activated ADP-ribosyltransferase, can mono-ADP-ribosylate double-stranded DNA ends. ADP-ribosylation of DNA mediated by PARP3 attaches a single mono-ADP-ribose moiety to the phosphate group at the terminal ends of DNA. We further show that mono ADP-ribosylation at DNA ends can be efficiently reversed by several cellular hydrolases (PARG, MACROD2, TARG1 and ARH3). This suggests that mono ADP-ribosylated DNA adducts can be efficiently removed in cells by several mechanisms.

Original publication

DOI

10.1111/febs.14297

Type

Journal article

Journal

FEBS J

Publication Date

12/2017

Volume

284

Pages

4002 - 4016

Keywords

ADP-ribose hydrolase, ADP-ribosylation, DNA, DNA repair, PARP, ADP-Ribosylation, Adenosine Diphosphate Ribose, Animals, Cell Cycle Proteins, DNA, DNA Breaks, DNA Repair, Humans, Hydrolases, Models, Genetic, NAD, Poly(ADP-ribose) Polymerases