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CK2 phosphorylates the scaffold protein XRCC1, which is required for efficient DNA single-strand break (SSB) repair. Here, we express an XRCC1 protein (XRCC1(ckm)) that cannot be phosphorylated by CK2 in XRCC1 mutated EM9 cells and show that the role of this post-translational modification gives distinct phenotypes in SSB repair and base excision repair (BER). Interestingly, we find that fewer SSBs are formed during BER after treatment with the alkylating agent dimethyl sulfate (DMS) in EM9 cells expressing XRCC1(ckm) (CKM cells) or following inhibition with the CK2 inhibitor 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole (DMAT). We also show that XRCC1(ckm) protein has a higher affinity for DNA than wild type XRCC1 protein and resides in an immobile fraction on DNA, in particular after damage. We propose a model whereby the increased affinity for DNA sequesters XRCC1(ckm) and the repair enzymes associated with it, at the repair site, which retards kinetics of BER. In conclusion, our results indicate that phosphorylation of XRCC1 by CK2 facilitates the BER incision step, likely by promoting dissociation from DNA.

Original publication

DOI

10.1016/j.dnarep.2011.07.004

Type

Journal article

Journal

DNA Repair (Amst)

Publication Date

05/09/2011

Volume

10

Pages

961 - 969

Keywords

Alkylating Agents, Animals, CHO Cells, Casein Kinase II, Cell Survival, Cricetinae, Cricetulus, DNA, DNA Breaks, Single-Stranded, DNA Repair, DNA-Binding Proteins, Gene Expression Regulation, Mutation Rate, Phosphorylation, Rad51 Recombinase, Sulfuric Acid Esters, Time Factors, X-ray Repair Cross Complementing Protein 1