Filling in the gaps in PARP inhibitor-induced synthetic lethality.


Tumors with loss of breast cancer type 1 susceptibility protein (BRCA1) are homologous recombination (HR) deficient and hypersensitive to poly(ADP-ribose) polymerase inhibitors (PARPi). However, these tumors may restore HR and acquire PARPi resistance via loss of end-protection of DNA double-strand breaks. We found that loss of nuclear DNA ligase III resensitizes HR-restored BRCA1-deficient cells to PARPi by exposing post-replicative single-stranded DNA (ssDNA) gaps. Our work, and that of others, identifies ssDNA gaps as a key determinant of PARPi response.

More about this publication

Molecular & cellular oncology
  • Volume 8
  • Issue nr. 6
  • Pages 2010512
  • Publication date 15-04-2022

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