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Genome-wide and high-density CRISPR-Cas9 screens identify point mutations in PARP1 causing PARP inhibitor resistance

Authors :
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
Source :
Nature Communications, Vol 9, Iss 1, Pp 1-14 (2018)
Publication Year :
2018
Publisher :
Nature Portfolio, 2018.

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.

Subjects

Subjects :
Science

Details

Language :
English
ISSN :
20411723
Volume :
9
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Nature Communications
Publication Type :
Academic Journal
Accession number :
edsdoj.1eb977c74fb546b0a7321e49be5d0643
Document Type :
article
Full Text :
https://doi.org/10.1038/s41467-018-03917-2