title: Distribution of protein poly(ADP-ribosyl)ation systems across all domains of life.
abstract: Poly(ADP-ribosyl)ation is a post-translational modification of proteins involved in regulation of many cellular pathways. Poly(ADP-ribose) (PAR) consists of chains of repeating ADP-ribose nucleotide units and is synthesized by the family of enzymes called poly(ADP-ribose) polymerases (PARPs). This modification can be removed by the hydrolytic action of poly(ADP-ribose) glycohydrolase (PARG) and ADP-ribosylhydrolase 3 (ARH3). Hydrolytic activity of macrodomain proteins (MacroD1, MacroD2 and TARG1) is responsible for the removal of terminal ADP-ribose unit and for complete reversion of protein ADP-ribosylation. Poly(ADP-ribosyl)ation is widely utilized in eukaryotes and PARPs are present in representatives from all six major eukaryotic supergroups, with only a small number of eukaryotic species that do not possess PARP genes. The last common ancestor of all eukaryotes possessed at least five types of PARP proteins that include both mono and poly(ADP-ribosyl) transferases. Distribution of PARGs strictly follows the distribution of PARP proteins in eukaryotic species. At least one of the macrodomain proteins that hydrolyse terminal ADP-ribose is also always present. Therefore, we can presume that the last common ancestor of all eukaryotes possessed a fully functional and reversible PAR metabolism and that PAR signalling provided the conditions essential for survival of the ancestral eukaryote in its ancient environment. PARP proteins are far less prevalent in bacteria and were probably gained through horizontal gene transfer. Only eleven bacterial species possess all proteins essential for a functional PAR metabolism, although it is not known whether PAR metabolism is truly functional in bacteria. Several dsDNA viruses also possess PARP homologues, while no PARP proteins have been identified in any archaeal genome. Our analysis of the distribution of enzymes involved in PAR metabolism provides insight into the evolution of these important signalling systems, as well as providing the basis for selection of the appropriate genetic model organisms to study the physiology of the specific human PARP proteins.
authors.affiliation: Division of Molecular Biology, Ruđer Bošković Institute, Zagreb 10002, Croatia.
authors.forename: Dragutin
authors.initials: D
authors.lastname: Perina
authors.affiliation: Division of Molecular Biology, Ruđer Bošković Institute, Zagreb 10002, Croatia.
authors.forename: Andreja
authors.initials: A
authors.lastname: Mikoč
authors.affiliation: Division of Molecular Biology, Ruđer Bošković Institute, Zagreb 10002, Croatia.
authors.forename: Josip
authors.initials: J
authors.lastname: Ahel
authors.affiliation: Division of Molecular Biology, Ruđer Bošković Institute, Zagreb 10002, Croatia.
authors.forename: Helena
authors.initials: H
authors.lastname: Ćetković
authors.affiliation: Division for Marine and Environmental Research, Ruđer Bošković Institute, Zagreb 10002, Croatia; Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
authors.forename: Roko
authors.initials: R
authors.lastname: Žaja
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK. Electronic address: ivan.ahel@path.ox.ac.uk.
authors.forename: Ivan
authors.initials: I
authors.lastname: Ahel
mesh_terms: D000818:Animals; D019843:Archaeal Proteins / Q000235:genetics / Q000378:metabolism; D020134:Catalytic Domain; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000737:chemistry / Q000378:metabolism; D005057:Eukaryotic Cells / Q000378:metabolism; D019143:Evolution, Molecular; D005399:Fishes; D006801:Humans; D006867:Hydrolases / Q000737:chemistry / Q000378:metabolism; D019476:Insect Proteins / Q000737:chemistry / Q000378:metabolism; D010802:Phylogeny; D010940:Plant Proteins / Q000737:chemistry / Q000378:metabolism; D011064:Poly Adenosine Diphosphate Ribose / Q000737:chemistry* / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000737:chemistry / Q000378:metabolism*; D011387:Prokaryotic Cells / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction; D038501:Tankyrases / Q000737:chemistry / Q000378:metabolism; D014780:Viruses / Q000235:genetics / Q000378:metabolism
chemical_list: D019843:Archaeal Proteins; D019476:Insect Proteins; C523332:MACROD2 protein, human; D010940:Plant Proteins; D011518:Proto-Oncogene Proteins; D011064:Poly Adenosine Diphosphate Ribose; C499627:PARP10 protein, human; C576117:PARP16 protein, human; D011065:Poly(ADP-ribose) Polymerases; D038501:Tankyrases; D006867:Hydrolases; D045643:DNA Repair Enzymes
keywords: DNA damage response; Macrodomain; PARG; PARP; Poly(ADP-ribose)