title: PARPs and the DNA damage response.
abstract: Adenosine diphosphate (ADP)-ribosylation is an important posttranslational modification catalyzed by a variety of enzymes, including poly (ADP ribose) polymerases (PARPs), which use nicotinamide adenine dinucleotide (NAD(+)) as a substrate to synthesize and transfer ADP-ribose units to acceptor proteins. The PARP family members possess a variety of structural domains, span a wide range of functions and localize to various cellular compartments. Among the molecular actions attributed to PARPs, their role in the DNA damage response (DDR) has been widely documented. In particular, PARPs 1-3 are involved in several cellular processes that respond to DNA lesions, which include DNA damage recognition, signaling and repair as well as local transcriptional blockage, chromatin remodeling and cell death induction. However, how these enzymes are able to participate in such numerous and diverse mechanisms in response to DNA damage is not fully understood. Herein, the DDR functions of PARPs 1-3 and the emerging roles of poly (ADP ribose) polymers in DNA damage are reviewed. The development of PARP inhibitors, their applications and mechanisms of action are also discussed in the context of the DDR.
authors.affiliation: Departamento de Biofísica, Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
authors.forename: Fabricio G
authors.initials: FG
authors.lastname: Sousa
authors.forename: Renata
authors.initials: R
authors.lastname: Matuo
authors.forename: Daniele G
authors.initials: DG
authors.lastname: Soares
authors.forename: Alexandre E
authors.initials: AE
authors.lastname: Escargueil
authors.forename: João A P
authors.initials: JA
authors.lastname: Henriques
authors.forename: Annette K
authors.initials: AK
authors.lastname: Larsen
authors.forename: Jenifer
authors.initials: J
authors.lastname: Saffi
mesh_terms: D000818:Animals; D004249:DNA Damage; D006801:Humans; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation
chemical_list: D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases