Nature Communications (May 2018)
Genome-wide and high-density CRISPR-Cas9 screens identify point mutations in PARP1 causing PARP inhibitor resistance
- Stephen J. Pettitt,
- Dragomir B. Krastev,
- Inger Brandsma,
- Amy Dréan,
- Feifei Song,
- Radoslav Aleksandrov,
- Maria I. Harrell,
- Malini Menon,
- Rachel Brough,
- James Campbell,
- Jessica Frankum,
- Michael Ranes,
- Helen N. Pemberton,
- Rumana Rafiq,
- Kerry Fenwick,
- Amanda Swain,
- Sebastian Guettler,
- Jung-Min Lee,
- Elizabeth M. Swisher,
- Stoyno Stoynov,
- Kosuke Yusa,
- Alan Ashworth,
- Christopher J. Lord
Affiliations
- Stephen J. Pettitt
- The CRUK Gene Function Laboratory, The Institute of Cancer Research
- Dragomir B. Krastev
- The CRUK Gene Function Laboratory, The Institute of Cancer Research
- Inger Brandsma
- The CRUK Gene Function Laboratory, The Institute of Cancer Research
- Amy Dréan
- The CRUK Gene Function Laboratory, The Institute of Cancer Research
- Feifei Song
- The CRUK Gene Function Laboratory, The Institute of Cancer Research
- Radoslav Aleksandrov
- Institute of Molecular Biology “Roumen Tsanev”, Bulgarian Academy of Sciences
- Maria I. Harrell
- University of Washington School of Medicine
- Malini Menon
- The CRUK Gene Function Laboratory, The Institute of Cancer Research
- Rachel Brough
- The CRUK Gene Function Laboratory, The Institute of Cancer Research
- James Campbell
- The CRUK Gene Function Laboratory, The Institute of Cancer Research
- Jessica Frankum
- The CRUK Gene Function Laboratory, The Institute of Cancer Research
- Michael Ranes
- Divison of Structural Biology, The Institute of Cancer Research
- Helen N. Pemberton
- The CRUK Gene Function Laboratory, The Institute of Cancer Research
- Rumana Rafiq
- The CRUK Gene Function Laboratory, The Institute of Cancer Research
- Kerry Fenwick
- Tumour Profiling Unit, The Institute of Cancer Research
- Amanda Swain
- Tumour Profiling Unit, The Institute of Cancer Research
- Sebastian Guettler
- Divison of Structural Biology, The Institute of Cancer Research
- Jung-Min Lee
- Center for Cancer Research, National Cancer Institute
- Elizabeth M. Swisher
- University of Washington School of Medicine
- Stoyno Stoynov
- Institute of Molecular Biology “Roumen Tsanev”, Bulgarian Academy of Sciences
- Kosuke Yusa
- Wellcome Trust Sanger Institute
- Alan Ashworth
- UCSF Helen Diller Family Comprehensive Cancer Center
- Christopher J. Lord
- The CRUK Gene Function Laboratory, The Institute of Cancer Research
- DOI
- https://doi.org/10.1038/s41467-018-03917-2
- Journal volume & issue
-
Vol. 9,
no. 1
pp. 1 – 14
Abstract
The mechanisms of PARP inhibitor (PARPi) resistance are poorly understood. Here the authors employ a CRISPR mutagenesis approach to identify PARP1 mutants causing PARPi resistance and find that PARP1 mutations are tolerated in BRCA1 mutated cells, suggesting alternative resistance mechanisms.
