title: The role of ADP-ribosylation in regulating DNA double-strand break repair.
abstract: ADP-ribosylation is the post translational modification of proteins catalysed by ADP-ribosyltransferases (ARTs). ADP-ribosylation has been implicated in a wide variety of cellular processes including cell growth and differentiation, apoptosis and transcriptional regulation. Perhaps the best characterised role, however, is in DNA repair and genome stability where ADP-ribosylation promotes resolution of DNA single strand breaks. Although ADP-ribosylation also occurs at DNA double strand breaks (DSBs), which ARTs catalyse this reaction and the molecular basis of how this modification regulates their repair remains a matter of debate. Here we review recent advances in our understanding of how ADP-ribosylation regulates DSB repair. Specifically, we highlight studies using the genetic model organism Dictyostelium, in addition to vertebrate cells that identify a third ART that accelerates DSB repair by non-homologous end-joining through promoting the interaction of repair factors with DNA lesions. The implications of these data with regards to how ADP-ribosylation regulates DNA repair and genome stability are discussed.
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford, UK.
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Pears
authors.forename: C Anne-Marie
authors.initials: CA
authors.lastname: Couto
authors.forename: Hong-Yu
authors.initials: HY
authors.lastname: Wang
authors.forename: Christine
authors.initials: C
authors.lastname: Borer
authors.forename: Rhian
authors.initials: R
authors.lastname: Kiely
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Lakin
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D004023:Dictyostelium / Q000378:metabolism; D042822:Genomic Instability; D006801:Humans; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D000244:Adenosine Diphosphate; C499320:PARP1 protein, human; C483041:PARP2 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases