Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase

@article{Bryant2005SpecificKO,
  title={Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase},
  author={Helen E. Bryant and Niklas Schultz and Huw D. Thomas and Kayan M. Parker and Dan Flower and Elena Lopez and Suzanne Kyle and Mark Meuth and Nicola J. Curtin and Thomas Helleday},
  journal={Nature},
  year={2005},
  volume={434},
  pages={913-917}
}
Poly(ADP-ribose) polymerase (PARP1) facilitates DNA repair by binding to DNA breaks and attracting DNA repair proteins to the site of damage. Nevertheless, PARP1-/- mice are viable, fertile and do not develop early onset tumours. Here, we show that PARP inhibitors trigger γ-H2AX and RAD51 foci formation. We propose that, in the absence of PARP1, spontaneous single-strand breaks collapse replication forks and trigger homologous recombination for repair. Furthermore, we show that BRCA2-deficient… 

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