Poly(ADP-ribose): novel functions for an old molecule

Abstract

The addition to proteins of the negatively charged polymer of ADP-ribose (PAR), which is synthesized by PAR polymerases (PARPs) from NAD(+), is a unique post-translational modification. It regulates not only cell survival and cell-death programmes, but also an increasing number of other biological functions with which novel members of the PARP family have been associated. These functions include transcriptional regulation, telomere cohesion and mitotic spindle formation during cell division, intracellular trafficking and energy metabolism.

La mort cellulaire programmée ne manque pas de vocabulaire

“…dans le fait qu'elles participent toutes en parallèle à la réalisation de ce programme de mort. D'autres signaux indépendants des récepteurs de mort peuvent conduire à la nécrose régulée, notamment par l'intermédiaire de l'activation de l'enzyme de réparation de l'ADN PARP-1 [13]. Des stress génotoxiques importants, pouvant découler d'un excès de ROS, comme dans le syndrome d'ischémie-reperfusion par exemple, en sont générale-ment responsables [14].…”

Small-Molecule Chemical Probe Rescues Cells from Mono-ADP-Ribosyltransferase ARTD10/PARP10-Induced Apoptosis and Sensitizes Cancer Cells to DNA Damage

“…While some ARTDs modify substrates by transferring iteratively multiple ADP-ribose units resulting in poly-ADP-ribosylation (PARylation), most ARTDs mono-ADP-ribosylate (MARylate) their substrates (Kleine et al, 2008). ARTDs function in DNA damage repair (Malanga and Althaus, 2005;Nicolae et al, 2014Nicolae et al, , 2015, the unfolded protein response (Jwa and Chang, 2012), apoptosis Koh et al, 2005), heat shock (Petesch and Lis, 2008), cellular signaling (Feijs et al, 2013a;, cell division (Chang et al, 2004(Chang et al, , 2005(Chang et al, , 2009Ha et al, 2012), as well as transcription and chromatin regulation Schreiber et al, 2006). PARylating ARTDs (pARTDs; ARTD1-6), most prominently ARTD1, have been the focus of cancer related research during the past two decades.…”

The macroPARP genes parp‐9 and parp‐14 are developmentally and differentially regulated in mouse tissues

“…Poly(ADP-ribosyl)ation is a post-translational modification of proteins mediated by one of the 17 members of the poly(ADP-ribose) polymerases (PARP; Amé et al, 2004;Schreiber et al, 2006). PARP-1, the founding member of the PARP family, is a molecular sensor of DNA breaks, playing a key role in the spatial and temporal organization of break repair through the local synthesis of poly(ADP-ribose) (PAR) at damaged sites.…”

“…PARP-1, the founding member of the PARP family, is a molecular sensor of DNA breaks, playing a key role in the spatial and temporal organization of break repair through the local synthesis of poly(ADP-ribose) (PAR) at damaged sites. In addition to its critical involvement in cellular response to DNA damage, poly(ADP-ribosyl)ation has been ascribed to regulate various biological processes such as transcription, mitotic segregation, telomere homeostasis, cell proliferation, transformation, and cell death (Schreiber et al, 2006). The diversity of PAR functions is a consequence of the variety of the functional domains combined to the PARP domain in each PARP family member.…”

“…This region is syntenically conserved in mouse chromosome region 16B3, with the exception of the PARP-15 gene, which is absent in mouse (and species other than primates, Schreiber et al, 2006). Moreover, PARP-9/BAL1 and BBAP genes are located head-to-head, their mRNAs are antisense through their 5Ј extremities, and both genes are controlled by a IFN␥-responsive bidirectional promoter (Juszczynski et al, 2006).…”