Nature Communications (Jul 2017)

Progression through mitosis promotes PARP inhibitor-induced cytotoxicity in homologous recombination-deficient cancer cells

  • Pepijn M. Schoonen,
  • Francien Talens,
  • Colin Stok,
  • Ewa Gogola,
  • Anne Margriet Heijink,
  • Peter Bouwman,
  • Floris Foijer,
  • Madalena Tarsounas,
  • Sohvi Blatter,
  • Jos Jonkers,
  • Sven Rottenberg,
  • Marcel A. T. M. van Vugt

DOI
https://doi.org/10.1038/ncomms15981
Journal volume & issue
Vol. 8, no. 1
pp. 1 – 13

Abstract

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Mutations in BRCA1 and BRCA2 render a cancer cell hypersensitive to PARP inhibitors but they can acquire resistance and relapse. Here the authors find that PARP inhibition leads to replication fork instability, cytokinesis failure and cell death, aiding our understanding of how inhibition leads to cytotoxic outcomes.