Nature Communications (Jul 2021)
Serine-linked PARP1 auto-modification controls PARP inhibitor response
- Evgeniia Prokhorova,
- Florian Zobel,
- Rebecca Smith,
- Siham Zentout,
- Ian Gibbs-Seymour,
- Kira Schützenhofer,
- Alessandra Peters,
- Joséphine Groslambert,
- Valentina Zorzini,
- Thomas Agnew,
- John Brognard,
- Michael L. Nielsen,
- Dragana Ahel,
- Sébastien Huet,
- Marcin J. Suskiewicz,
- Ivan Ahel
Affiliations
- Evgeniia Prokhorova
- Sir William Dunn School of Pathology, University of Oxford
- Florian Zobel
- Sir William Dunn School of Pathology, University of Oxford
- Rebecca Smith
- Univ Rennes, CNRS, Structure Fédérative de Recherche Biosit, IGDR (Institut de Génétique et Développement de Rennes) – UMR 6290
- Siham Zentout
- Univ Rennes, CNRS, Structure Fédérative de Recherche Biosit, IGDR (Institut de Génétique et Développement de Rennes) – UMR 6290
- Ian Gibbs-Seymour
- Sir William Dunn School of Pathology, University of Oxford
- Kira Schützenhofer
- Sir William Dunn School of Pathology, University of Oxford
- Alessandra Peters
- Sir William Dunn School of Pathology, University of Oxford
- Joséphine Groslambert
- Sir William Dunn School of Pathology, University of Oxford
- Valentina Zorzini
- Sir William Dunn School of Pathology, University of Oxford
- Thomas Agnew
- Sir William Dunn School of Pathology, University of Oxford
- John Brognard
- Laboratory of Cell and Developmental Signaling, Center for Cancer Research, National Cancer Institute
- Michael L. Nielsen
- Proteomics Program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen
- Dragana Ahel
- Sir William Dunn School of Pathology, University of Oxford
- Sébastien Huet
- Univ Rennes, CNRS, Structure Fédérative de Recherche Biosit, IGDR (Institut de Génétique et Développement de Rennes) – UMR 6290
- Marcin J. Suskiewicz
- Sir William Dunn School of Pathology, University of Oxford
- Ivan Ahel
- Sir William Dunn School of Pathology, University of Oxford
- DOI
- https://doi.org/10.1038/s41467-021-24361-9
- Journal volume & issue
-
Vol. 12,
no. 1
pp. 1 – 12
Abstract
PARP inhibitors function by trapping PARP1 protein on DNA breaks, which has cytotoxic consequences to cancer cells. Here the authors identify three serine residues within PARP1 as key sites whose efficient HPF1-dependent modification counters PARP1 trapping and contributes to inhibitor tolerance.
