title: The rise and fall of poly(ADP-ribose): An enzymatic perspective.
abstract: Human cells respond to DNA damage with an acute and transient burst in production of poly(ADP-ribose), a posttranslational modification that expedites damage repair and plays a pivotal role in cell fate decisions. Poly(ADP-ribose) polymerases (PARPs) and glycohydrolase (PARG) are the key set of enzymes that orchestrate the rise and fall in cellular levels of poly(ADP-ribose). In this perspective, we focus on recent structural and mechanistic insights into the enzymes involved in poly(ADP-ribose) production and turnover, and we highlight important questions that remain to be answered.
authors.affiliation: Department of Biochemistry & Molecular Biology, Sydney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA. Electronic address: john.pascal@jefferson.edu.
authors.forename: John M
authors.initials: JM
authors.lastname: Pascal
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, Saint Louis, MO 63110, USA. Electronic address: tome@biochem.wustl.edu.
authors.forename: Tom
authors.initials: T
authors.lastname: Ellenberger
mesh_terms: D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D006026:Glycoside Hydrolases / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D011064:Poly Adenosine Diphosphate Ribose / Q000737:chemistry* / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000737:chemistry* / Q000378:metabolism; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013379:Substrate Specificity
chemical_list: D007527:Isoenzymes; D011064:Poly Adenosine Diphosphate Ribose; D004247:DNA; D011065:Poly(ADP-ribose) Polymerases; D006026:Glycoside Hydrolases
keywords: ADP-ribose; DNA damage response; MARG; PARG; PARP; Poly(ADP-ribose)