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Reversible mono‐ADP‐ribosylation of DNA breaks
Author(s) -
Munnur Deeksha,
Ahel Ivan
Publication year - 2017
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.14297
Subject(s) - adp ribosylation , nad+ kinase , biochemistry , dna , dna repair , nicotinamide adenine dinucleotide , dna damage , chromatin , polymerase , cofactor , biology , chemistry , poly adp ribose polymerase , adenosine diphosphate , microbiology and biotechnology , enzyme , platelet , platelet aggregation , immunology
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.