The expanding role of poly(ADP-ribose) metabolism: current challenges and new perspectives.
Recent discoveries have resulted in significant breakthroughs in the understanding of PARPs and PARG functions within a broad range of cellular processes. The novel and sometimes unexpected pathways that are regulated by poly(ADP-ribosylation) bring new questions and hypotheses, some of them being contentious. In this review, we highlight current areas of investigation such as the clinical potential of PARP and PARG inhibitors and the important mitotic regulatory functions of poly(ADP-ribose) in cell-cycle progression, a recent discovery that has broadened our knowledge regarding poly(ADP-ribose) functions. A special emphasis is placed on recent advances in relation to PARG that are stimulating new directions in future research. Noticeably, the existence of various PARG isoforms characterized by distinct cellular localizations and nucleocytoplasmic shuttling properties challenges our current comprehension of pADPr metabolism. Observations and suppositions towards functionally important regulatory elements in the N-terminal portion of PARG are also discussed.
Gagné
Jean-Philippe
JP
Health and Environment Unit, Laval University Medical Research Center, CHUQ, Faculty of Medicine, Laval University, 2705 Boulevard Laurier, Ste-Foy, Québec G1V 4G2, Canada.
Hendzel
Michael J
MJ
Droit
Arnaud
A
Poirier
Guy G
GG
D000818:Animals; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology; D004249:DNA Damage / Q000502:physiology; D006026:Glycoside Hydrolases / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*
D011064:Poly Adenosine Diphosphate Ribose; D006026:Glycoside Hydrolases; C022407:poly ADP-ribose glycohydrolase; D020169:Caspases