title: PARP and CSB modulate the processing of transcription-mediated DNA strand breaks.
abstract: Topoisomerase 1 (Top1)-DNA cleavage complexes induced by camptothecin (CPT) cause DNA strand breaks during DNA replication or transcription. Although the cellular responses to replication-mediated DNA double-strand breaks have been well studied, the responses to transcription-mediated DNA strand breaks have not. Here, we show that poly (ADP-ribose) polymerase (PARP) and cockayne syndrome group B protein (CSB) modulate the CPT-induced formation of discrete p53-binding protein 1 (53BP1) nuclear foci at sites of transcription-mediated DNA strand breaks. Inhibition of PARP activity enhanced the formation of these foci, while knockdown of essential components of the base excision repair (BER) pathway did not. These findings suggest that PARP suppresses transcription-mediated 53BP1 foci formation, but that this does not occur through the BER pathway. In addition, knockdown of CSB, one of the key factors of transcription-coupled repair, slowed the kinetics of 53BP1 foci formation. These data suggest that PARP and CSB modulate the formation of 53BP1 foci during the processing of transcription-mediated DNA strand breaks.
authors.affiliation: Innovative Anticancer Strategy for Therapeutics and Diagnosis Group, Innovation Center for Medical Redox Navigation, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Sakai
authors.forename: Ryo
authors.initials: R
authors.lastname: Sakasai
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kakeji
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kitao
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara
mesh_terms: D002166:Camptothecin / Q000633:toxicity; D045744:Cell Line, Tumor; D053903:DNA Breaks, Double-Stranded; D004265:DNA Helicases / Q000378:metabolism*; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*; D000075223:Poly-ADP-Ribose Binding Proteins; D034741:RNA, Small Interfering; D059004:Topoisomerase I Inhibitors / Q000633:toxicity; D014158:Transcription, Genetic; D000071857:Tumor Suppressor p53-Binding Protein 1
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D034741:RNA, Small Interfering; C498301:TP53BP1 protein, human; D059004:Topoisomerase I Inhibitors; D000071857:Tumor Suppressor p53-Binding Protein 1; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D004265:DNA Helicases; C078673:ERCC6 protein, human; D045643:DNA Repair Enzymes; D002166:Camptothecin