Role of cAMP-dependent protein kinase in the regulation of DNA repair.
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.
Lee
C H
CH
Department of Medicine, UMDNJ--Robert Wood Johnson Medical School, Piscataway, NJ, USA.
Sidik
K
K
Chin
K V
KV
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D002474:Cell-Free System; D000242:Cyclic AMP / Q000378:metabolism; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D004247:DNA / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects / Q000502:physiology*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007106:Immune Sera; D007546:Isoquinolines / Q000494:pharmacology; D012568:Schizosaccharomyces / Q000737:chemistry; D015398:Signal Transduction / Q000502:physiology; D013449:Sulfonamides
D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; D004791:Enzyme Inhibitors; D007106:Immune Sera; D007546:Isoquinolines; D013449:Sulfonamides; D015124:8-Bromo Cyclic Adenosine Monophosphate; D004247:DNA; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide