Abstract
Enhanced DNA repair is an important factor in drug resistance in cancer. Using cell-free extracts derived from the fission yeast, Schizosaccharomyces pombe, we demonstrate in an in vitro system DNA repair system that increased cAMP levels, which activates cAMP-dependent protein kinase (PKA), inhibits repair of ultraviolet (UV)-damaged DNA. Supplementing the cell-free system with the catalytic kinase subunit of PKA also inhibits DNA repair. In contrast, addition of the PKA inhibitor H-89 enhances repair activity. These results show that PKA regulates DNA repair synthesis, thus implicating the cAMP signaling pathway in DNA damage response and repair of UV-damaged DNA lesions.
MeSH terms
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8-Bromo Cyclic Adenosine Monophosphate / pharmacology
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Cell-Free System
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Cyclic AMP / metabolism
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Cyclic AMP-Dependent Protein Kinase RIalpha Subunit
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Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
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Cyclic AMP-Dependent Protein Kinases / immunology
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Cyclic AMP-Dependent Protein Kinases / metabolism
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Cyclic AMP-Dependent Protein Kinases / physiology*
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DNA / radiation effects
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DNA Damage
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DNA Repair / drug effects
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DNA Repair / physiology*
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Enzyme Activation
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Enzyme Inhibitors / pharmacology
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Immune Sera
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Isoquinolines / pharmacology
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Schizosaccharomyces / chemistry
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Signal Transduction / physiology
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Sulfonamides*
Substances
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Cyclic AMP-Dependent Protein Kinase RIalpha Subunit
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Enzyme Inhibitors
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Immune Sera
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Isoquinolines
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Sulfonamides
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8-Bromo Cyclic Adenosine Monophosphate
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DNA
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Cyclic AMP
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Cyclic AMP-Dependent Protein Kinases
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N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide