G-quadruplexes (G4) are naturally occurring DNA structures that stall replication forks. Homologous recombination (HR)stabilizes and restarts stalled replication forks and also repairs double-strand breaks (DSBs) that can form at these sites. Zimmer et al. show that the G4-stabilizing compound pyridostatin (PDS) induced DSB accumulation in HR-deficient cells, which in turn reduced their proliferation. HR-defective cellswith certain types of resistance to the poly(ADP) ribose polymerase (PARP) inhibitor olaparib were also sensitive to PDS. This suggests that G4-stabilizing drugs could selectively target HR-defective tumour cells.
References
Zimmer, J. et al. Targeting BRCA1 and BRCA2 deficiencies with G-quadruplex-interacting compounds. Mol. Cell http://dx.doi.org/10.1016/j.molcel.2015.12.004 (2015)
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Alderton, G. Targeting replication fork stalling. Nat Rev Cancer 16, 70 (2016). https://doi.org/10.1038/nrc.2016.10
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DOI: https://doi.org/10.1038/nrc.2016.10
