Inhibition of poly(ADP-ribose) polymerase down-regulates BRCA1 and RAD51 in a pathway mediated by E2F4 and p130.

@article{Hegan2010InhibitionOP,
  title={Inhibition of poly(ADP-ribose) polymerase down-regulates BRCA1 and RAD51 in a pathway mediated by E2F4 and p130.},
  author={Denise Campisi Hegan and Yuhong Lu and Gregory C. Stachelek and Meredith E. Crosby and Ranjit S Bindra and Peter M. Glazer},
  journal={Proceedings of the National Academy of Sciences of the United States of America},
  year={2010},
  volume={107 5},
  pages={2201-6}
}
Inhibitors of poly(ADP-ribose) polymerase (PARP) are in clinical trials for cancer therapy, on the basis of the role of PARP in recruitment of base excision repair (BER) factors to sites of DNA damage. Here we show that PARP inhibition to block BER is toxic to hypoxic cancer cells, in which homology-dependent repair (HDR) is known to be down-regulated. However, we also report the unexpected finding that disruption of PARP, itself, either via chemical PARP inhibitors or siRNAs targeted to PARP-1… CONTINUE READING
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