Protein kinase CK2 is required for the recruitment of 53BP1 to sites of DNA double-strand break induced by radiomimetic drugs

Barbara Guerra; Kuniyoshi Iwabuchi; Olaf-Georg Issinger

doi:10.1016/j.canlet.2013.11.008

Protein kinase CK2 is required for the recruitment of 53BP1 to sites of DNA double-strand break induced by radiomimetic drugs

Cancer Lett. 2014 Apr 1;345(1):115-23. doi: 10.1016/j.canlet.2013.11.008. Epub 2013 Dec 11.

Authors

Barbara Guerra¹, Kuniyoshi Iwabuchi², Olaf-Georg Issinger³

Affiliations

¹ Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark. Electronic address: [email protected].
² Department of Biochemistry, Kanazawa Medical University, Ishikawa, Japan.
³ Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark.

PMID: 24333722
DOI: 10.1016/j.canlet.2013.11.008

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.

Keywords: 53BP1; ATM; CK2; DNA damage; Glioblastoma cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / pharmacology*
Casein Kinase II / deficiency
Casein Kinase II / genetics
Casein Kinase II / metabolism*
Cell Line, Tumor
DNA Breaks, Double-Stranded*
DNA End-Joining Repair
DNA, Neoplasm / drug effects
DNA, Neoplasm / genetics
Glioblastoma / drug therapy
Glioblastoma / enzymology
Glioblastoma / genetics
Glioblastoma / metabolism*
Humans
Intracellular Signaling Peptides and Proteins / genetics
Intracellular Signaling Peptides and Proteins / metabolism*
Phosphorylation
RNA, Small Interfering / administration & dosage
RNA, Small Interfering / genetics
Radiation Dosage
Radiation Effects
Signal Transduction
Transfection
Tumor Suppressor p53-Binding Protein 1

Substances

Antineoplastic Agents
DNA, Neoplasm
Intracellular Signaling Peptides and Proteins
RNA, Small Interfering
TP53BP1 protein, human
Tumor Suppressor p53-Binding Protein 1
Casein Kinase II