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.

Keywords: DNA damage response; Macrodomain; PARG; PARP; Poly(ADP-ribose).

Fig. 1

Schematic architecture of domains present in PARP representatives. PARPs belonging to six clades are assorted in six panels (A–E). Numbers indicate amino acids. Proteins are represented in a scale 1:10 (1 mm = 10 amino acids). Protein domains have been indicated with coloured boxes and each protein has been searched against SMART/Pfam databases. Abbreviations of domain names are retrieved from SMART/Pfam databases and indicated in figure. Shortened names include: ZnF (red and pink), DNA-binding zinc finger domains Zf-PARP and PADR1, respectively; A, Ankyrin (ANK); T, transmembrane region (TM); ZF, RNA-binding zinc finger ZnF_C3H1; U, ubiquitin-interacting motif (UIM); Domains which are not retrieved from SMART/Pfam databases: NBD, nucleic acid binding domain according to . CRR, cysteine-rich region with putative zinc finger.

Fig. 2

Domain architecture of PARG and bactPARG enzymes. Abbreviations of domain names are retrieved from SMART/Pfam databases and indicated in figure. Domains which are not retrieved from SMART/Pfam databases: Z (red and pink), represent Zn finger motifs, poly(ADP-ribose)-binding Zn finger (PBZ) in A. vaga and polyA-RNA-binding Nab2-type of ZnF in E. dispar, respectively.

Fig. 3

Domain architecture of human ARH3 and ARH3-like proteins from representative species. Abbreviations of domain names are retrieved from SMART/Pfam databases and indicated in figure. Shortened names include: ZnF (red and pink), ZnF-RBZ in A. castellanii and Zf-UBP in C. owczarzaki ARH3-like, respectively.