Abstract
Cellular responses to DNA damage are orchestrated by the large phosphoinositol-3-kinase related kinases ATM, ATR and DNA-PK. We have developed a cell-free system to dissect the biochemical mechanisms of these kinases. Using this system, we identify heterogeneous nuclear ribonucleoprotein U (hnRNP-U), also termed scaffold attachment factor A (SAF-A), as a specific substrate for DNA-PK. We show that hnRNP-U is phosphorylated at Ser59 by DNA-PK in vitro and in cells in response to DNA double-strand breaks. Phosphorylation of hnRNP-U suggests novel functions for DNA-PK in the response to DNA damage.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Ataxia Telangiectasia Mutated Proteins
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Cell Cycle Proteins / metabolism
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Cell Line, Tumor
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Cell-Free System / enzymology
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Checkpoint Kinase 1
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DNA Breaks, Double-Stranded*
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DNA-Activated Protein Kinase / metabolism*
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DNA-Binding Proteins / metabolism
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Enzyme Activation
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Heterogeneous-Nuclear Ribonucleoprotein U / metabolism*
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Humans
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Molecular Sequence Data
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Phosphorylation
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Poly dA-dT / metabolism
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Protein Kinases / metabolism
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Protein Serine-Threonine Kinases / metabolism
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Serine / metabolism*
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Tumor Suppressor Proteins / metabolism
Substances
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Cell Cycle Proteins
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DNA-Binding Proteins
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Heterogeneous-Nuclear Ribonucleoprotein U
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Tumor Suppressor Proteins
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Poly dA-dT
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Serine
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Protein Kinases
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ATM protein, human
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ATR protein, human
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Ataxia Telangiectasia Mutated Proteins
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Checkpoint Kinase 1
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DNA-Activated Protein Kinase
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Protein Serine-Threonine Kinases