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DNA REPAIR

Unsprung traps keep PARP inhibitors effective

Nature Cell Biology volume 24, pages 2–4 (2022)Cite this article

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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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Fig. 1: Key molecular events that lead to the release of trapped PARP1 from DNA.

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Authors and Affiliations

  1. Departments of Biochemistry and Molecular Biology and Oncology, Robson DNA Science Centre, Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada

    Peter M. Brownlee, Luc Provencher & Aaron A. Goodarzi

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  1. Peter M. Brownlee
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  2. Luc Provencher
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  3. Aaron A. Goodarzi
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Contributions

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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Correspondence to Aaron A. Goodarzi.

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The authors declare no competing interests.

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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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