Replication Fork Stability Confers Chemoresistance in BRCA-deficient Cells

  title={Replication Fork Stability Confers Chemoresistance in BRCA-deficient Cells},
  author={Arnab Ray Chaudhuri and Elsa Call{\'e}n and Xia Ding and Ewa Gogola and Alexandra Alves Duarte and Ji-Eun Lee and Nancy Wong and Vanessa Lafarga and Jennifer A. Calvo and Nicholas J. Panzarino and S Rose John and Amanda M. Day and Anna Vidal Crespo and Binghui Shen and Linda Marie Starnes and Julian R. de Ruiter and Jeremy A Daniel and Panagiotis Konstantinopoulos and David Cortez and Sharon B Cantor and Oscar Fern{\'a}ndez-Capetillo and Kai Ge and Jos Jonkers and Sven Rottenberg and S. Kowshik Sharan and Andr{\'e} Nussenzweig},
Cells deficient in the Brca1 and Brca2 genes have reduced capacity to repair DNA double-strand breaks by homologous recombination and consequently are hypersensitive to DNA-damaging agents, including cisplatin and poly(ADP-ribose) polymerase (PARP) inhibitors. Here we show that loss of the MLL3/4 complex protein, PTIP, protects Brca1/2-deficient cells from DNA damage and rescues the lethality of Brca2-deficient embryonic stem cells. However, PTIP deficiency does not restore homologous… CONTINUE READING
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