title: A family of macrodomain proteins reverses cellular mono-ADP-ribosylation.
abstract: ADP-ribosylation is a reversible post-translational modification with wide-ranging biological functions in all kingdoms of life. A variety of enzymes use NAD(+) to transfer either single or multiple ADP-ribose (ADPr) moieties onto distinct amino acid substrates, often in response to DNA damage or other stresses. Poly-ADPr-glycohydrolase readily reverses poly-ADP-ribosylation induced by the DNA-damage sensor PARP1 and other enzymes, but it does not remove the most proximal ADPr linked to the target amino acid. Searches for enzymes capable of fully reversing cellular mono-ADP-ribosylation back to the unmodified state have proved elusive, which leaves a gap in the understanding of this modification. Here, we identify a family of macrodomain enzymes present in viruses, yeast and animals that reverse cellular ADP-ribosylation by acting on mono-ADP-ribosylated substrates. Our discoveries establish the complete reversibility of PARP-catalyzed cellular ADP-ribosylation as a regulatory modification.
authors.affiliation: Butenandt Institute of Physiological Chemistry, Ludwig Maximilians University of Munich, Munich, Germany.
authors.forename: Gytis
authors.initials: G
authors.lastname: Jankevicius
authors.forename: Markus
authors.initials: M
authors.lastname: Hassler
authors.forename: Barbara
authors.initials: B
authors.lastname: Golia
authors.forename: Vladimir
authors.initials: V
authors.lastname: Rybin
authors.forename: Martin
authors.initials: M
authors.lastname: Zacharias
authors.forename: Gyula
authors.initials: G
authors.lastname: Timinszky
authors.forename: Andreas G
authors.initials: AG
authors.lastname: Ladurner
mesh_terms: D000246:Adenosine Diphosphate Ribose / Q000378:metabolism*; D000595:Amino Acid Sequence; D055162:Biocatalysis; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009699:N-Glycosyl Hydrolases / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
chemical_list: D011506:Proteins; D000246:Adenosine Diphosphate Ribose; D009699:N-Glycosyl Hydrolases; C046422:ADP-ribosylarginine hydrolase