title: Protein kinase CK2 is required for the recruitment of 53BP1 to sites of DNA double-strand break induced by radiomimetic drugs.
abstract: The ataxia telangiectasia mutated (ATM) signaling pathway responds rapidly to DNA double-strand breaks (DSBs) and it is characterized by recruitment of sensor, mediator, transducer and repair proteins to sites of DNA damage. Data suggest that CK2 is implicated in the early cellular response to DSBs. We demonstrate that CK2 binds constitutively the adaptor protein 53BP1 through the tandem Tudor domains and that the interaction is disrupted upon induction of DNA damage. Down-regulation of CK2 results in significant reduction of (i) 53BP1 foci formation, (ii) binding to dimethylated histone H4 and (iii) ATM autophosphorylation. Our data suggest that CK2 is required for 53BP1 accumulation at sites of DSBs which is a prerequisite for efficient activation of the ATM-mediated signaling pathway.
authors: Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark. Electronic address: bag@bmb.sdu.dk.
authors: Barbara
authors: B
authors: Guerra
authors: Department of Biochemistry, Kanazawa Medical University, Ishikawa, Japan.
authors: Kuniyoshi
authors: K
authors: Iwabuchi
authors: Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark.
authors: Olaf-Georg
authors: OG
authors: Issinger
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D047390:Casein Kinase II / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D053903:DNA Breaks, Double-Stranded; D059766:DNA End-Joining Repair; D004273:DNA, Neoplasm / Q000187:drug effects / Q000235:genetics; D005909:Glioblastoma / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D011829:Radiation Dosage; D011830:Radiation Effects; D015398:Signal Transduction; D014162:Transfection; D000071857:Tumor Suppressor p53-Binding Protein 1
chemical_list: D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D047908:Intracellular Signaling Peptides and Proteins; D034741:RNA, Small Interfering; C498301:TP53BP1 protein, human; D000071857:Tumor Suppressor p53-Binding Protein 1; D047390:Casein Kinase II
keywords: 53BP1; ATM; CK2; DNA damage; Glioblastoma cells