Abstract
CK2 was the first protein kinase identified and is required for the proliferation and survival of mammalian cells. Here, we have identified an unanticipated role for CK2. We show that this essential protein kinase phosphorylates the scaffold protein XRCC1 and thereby enables the assembly and activity of DNA single-strand break repair protein complexes in vitro and at sites of chromosomal breakage. Moreover, we show that inhibiting XRCC1 phosphorylation by mutation of the CK2 phosphorylation sites or preventing CK2 activity using a highly specific inhibitor ablates the rapid repair of cellular DNA single-strand breaks by XRCC1. These data identify a direct role for CK2 in the repair of chromosomal DNA strand breaks and in maintaining genetic integrity.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Binding Sites / genetics
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CHO Cells
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Casein Kinase II
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Chromosomes / enzymology*
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Chromosomes / genetics
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Cricetinae
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DNA Damage / genetics*
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DNA Repair / drug effects
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DNA Repair / genetics*
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DNA, Single-Stranded / genetics*
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DNA-Binding Proteins / metabolism*
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Enzyme Inhibitors / pharmacology
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Humans
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Mutation / genetics
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Phosphorylation / drug effects
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Polynucleotide 5'-Hydroxyl-Kinase / genetics
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Polynucleotide 5'-Hydroxyl-Kinase / metabolism
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Protein Serine-Threonine Kinases / antagonists & inhibitors
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism*
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Protein Structure, Tertiary / genetics
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X-ray Repair Cross Complementing Protein 1
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Yeasts / enzymology
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Yeasts / genetics
Substances
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DNA, Single-Stranded
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DNA-Binding Proteins
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Enzyme Inhibitors
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X-ray Repair Cross Complementing Protein 1
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XRCC1 protein, human
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Polynucleotide 5'-Hydroxyl-Kinase
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Casein Kinase II
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Protein Serine-Threonine Kinases