The role of DNA-damage-response poly (ADP-ribose) polymerases on p53 activation after genotoxic treatment.

摘要

One of the earliest events in the response to genotoxic treatment is activation of the DNA-dependent poly(ADP-ribose) polymerases-1 and -2 (PARP-1 and PARP-2) enzymes. The functional interaction between tumour suppressor protein p53, the key protein to genomic maintenance, and PARPs is hypothesized to be either direct or via stimulation of ataxia-telangiectasia mutated (ATM) protein. Here we have analyzed p53 stabilization and activation/phosphorylation induced with hydrogen peroxide and doxorubicin in MCF-7 human cells following shRNA-mediated depletion of PARP-1 or PARP-2. The absence of PARP-2 decreases p53 activation following both genotoxic treatments, while absence PARP-1 decreases p53 accumulation following hydrogen peroxide treatment only. The cell cycle analysis following Dox treatment shows that absence of PARP-1 triggers a p53-independent G2/M-arrest, while absence of PARP-2 abrogates p53-mediated G 1-arrest. This study shows that PARP-2 is an inducer of p53 activation