PARP-mediated proteasome activation: a co-ordination of DNA repair and protein degradation?
During the evolution of aerobic life, antioxidant defence systems developed that either directly prevent oxidative modifications of the cellular constituents or remove the modified components. An example of the latter is the proteasome, which removes cytosolic oxidised proteins. Recently, a novel mechanism of activation of the nuclear 20S proteasome was discovered: automodified poly-(ADP-ribose) polymerase-1 (PARP-1) activates the proteasome to facilitate selective degradation of oxidatively damaged histones. Since activation of the PARP-1 itself is induced by DNA damage and is supposed to play a role in DNA repair, these new results suggest a joint role of PARP-1 in the removal of oxidised nucleoproteins and in DNA repair. We hypothesise that PARP-1 could provide a co-ordinative link between two nuclear antioxidant defence systems, whose concerted activation would produce a fast and efficient restoration of the native chromatin structure following oxidative stress.
Arnold
Jenny
J
Neuroscience Research Center, Medical Faculty (Charité), Humboldt University Berlin, Germany.
Grune
Tilman
T
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D004789:Enzyme Activation; D009097:Multienzyme Complexes / Q000378:metabolism*; D018384:Oxidative Stress; D046988:Proteasome Endopeptidase Complex; D011506:Proteins / Q000378:metabolism*
D009097:Multienzyme Complexes; D011506:Proteins; D004247:DNA; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex