Understanding how cancers react to poly(ADP-ribose) polymerase (PARP) trapping on DNA is crucial to thwart PARP inhibitor resistance. A recent study finds that trapped PARP1 is removed via the ubiquitin-dependent segregase p97, and that perturbing this molecular cascade increases PARP inhibitor cytotoxicity.
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P.M.B. and L.P. contributed equally to this News and Views. A.A.G. is the Canada Research Chair for Radiation Exposure Disease and this work was undertaken, in part, thanks to funding from the Canada Research Chairs program.
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Brownlee, P.M., Provencher, L. & Goodarzi, A.A. Unsprung traps keep PARP inhibitors effective. Nat Cell Biol 24, 2–4 (2022). https://doi.org/10.1038/s41556-021-00819-2
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DOI: https://doi.org/10.1038/s41556-021-00819-2
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