Evolutionary history of the poly(ADP-ribose) polymerase gene family in eukaryotes

Abstract

BackgroundThe Poly(ADP-ribose)polymerase (PARP) superfamily was originally identified as enzymes that catalyze the attachment of ADP-ribose subunits to target proteins using NAD+ as a substrate. The family is characterized by the catalytic site, termed the PARP signature. While these proteins can be found in a range of eukaryotes, they have been best studied in mammals. In these organisms, PARPs have key functions in DNA repair, genome integrity and epigenetic regulation. More recently it has been found that proteins within the PARP superfamily have altered catalytic sites, and have mono(ADP-ribose) transferase (mART) activity or are enzymatically inactive. These findings suggest that the PARP signature has a broader range of functions that initially predicted. In this study, we investigate the evolutionary history of PARP genes across the eukaryotes.ResultsWe identified in silico 236 PARP proteins from 77 species across five of the six eukaryotic supergroups. We performed extensive phylogenetic analyses of the identified PARPs. They are found in all eukaryotic supergroups for which sequence is available, but some individual lineages within supergroups have independently lost these genes. The PARP superfamily can be subdivided into six clades. Two of these clades were likely found in the last common eukaryotic ancestor. In addition, we have identified PARPs in organisms in which they have not previously been described.ConclusionsThree main conclusions can be drawn from our study. First, the broad distribution and pattern of representation of PARP genes indicates that the ancestor of all extant eukaryotes encoded proteins of this type. Second, the ancestral PARP proteins had different functions and activities. One of these proteins was similar to human PARP1 and likely functioned in DNA damage response. The second of the ancestral PARPs had already evolved differences in its catalytic domain that suggest that these proteins may not have possessed poly(ADP-ribosyl)ation activity. Third, the diversity of the PARP superfamily is larger than previously documented, suggesting as more eukaryotic genomes become available, this gene family will grow in both number and type.

Identification of novel components of NAD-utilizing metabolic pathways and prediction of their biochemical functions

“…Such a PARP precursor and also certain sirtuins appear to have been already acquired prior to the last eukaryotic common ancestor, perhaps from endosymbiotic bacteria, giving rise to the histonedeacetylation and polyADP-ribosylation systems seen in eukaryotes. 94,102 Further Sirtuin, Macro, NADAR, NUE, and ART domains appear to have also been repeatedly acquired by eukaryotes in their subsequent evolution and incorporated into diverse functional systems distinct from those of the ancestral bacterial versions. The NEURL4 clade of BC4486-related ARTs represents a potential independent transfer that probably happened well after the last-eukaryotic common ancestor but prior to divergence of several major eukaryotic lineages, such as opisthokonts and alveolates.…”

PARP12, an Interferon-stimulated Gene Involved in the Control of Protein Translation and Inflammation

“…Poly(ADP-ribose) polymerases (PARPs) 3 represent a family of enzymes present in almost all nucleated cells of mammals, plants, lower eukaryotes (with the notable exception of yeasts), as well as eubacteria, archaebacteria, and double-stranded DNA viruses (1,2). PARPs catalyze the transfer of negatively charged ADP-ribose subunits to target proteins using NAD ϩ as a substrate.…”

Recognition and Repair Pathways of Damaged DNA in Higher Plants

“…The motif also functions as the main interface for protein-protein interactions. Finally, at its COOH-terminal region, PARP1 has motifs with different catalytic activities including NAD + hydrolysis as well as initiation, elongation, branching and termination of ADP-ribose polymers (Citarelli et al, 2010). It has been shown in mammalian cells that, upon binding a DNA lesion PARP1 poly(ADP)ribosylates itself as well as nearby histones (H1 and H2B), which relaxes the chromatin structure allowing better access for XRCC1 and other repair proteins to the damaged site (Poirier et al, 1982;Masson et al, 1998;Pleschke et al, 2000).…”