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

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.

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Autores principales: 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
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Lenguaje:EN
Publicado: Nature Portfolio 2018
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Acceso en línea:https://doaj.org/article/1eb977c74fb546b0a7321e49be5d0643
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spelling oai:doaj.org-article:1eb977c74fb546b0a7321e49be5d06432021-12-02T16:49:32ZGenome-wide and high-density CRISPR-Cas9 screens identify point mutations in PARP1 causing PARP inhibitor resistance10.1038/s41467-018-03917-22041-1723https://doaj.org/article/1eb977c74fb546b0a7321e49be5d06432018-05-01T00:00:00Zhttps://doi.org/10.1038/s41467-018-03917-2https://doaj.org/toc/2041-1723The 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.Stephen J. PettittDragomir B. KrastevInger BrandsmaAmy DréanFeifei SongRadoslav AleksandrovMaria I. HarrellMalini MenonRachel BroughJames CampbellJessica FrankumMichael RanesHelen N. PembertonRumana RafiqKerry FenwickAmanda SwainSebastian GuettlerJung-Min LeeElizabeth M. SwisherStoyno StoynovKosuke YusaAlan AshworthChristopher J. LordNature PortfolioarticleScienceQENNature Communications, Vol 9, Iss 1, Pp 1-14 (2018)
institution DOAJ
collection DOAJ
language EN
topic Science
Q
spellingShingle Science
Q
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
Genome-wide and high-density CRISPR-Cas9 screens identify point mutations in PARP1 causing PARP inhibitor resistance
description 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.
format article
author 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
author_facet 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
author_sort Stephen J. Pettitt
title Genome-wide and high-density CRISPR-Cas9 screens identify point mutations in PARP1 causing PARP inhibitor resistance
title_short Genome-wide and high-density CRISPR-Cas9 screens identify point mutations in PARP1 causing PARP inhibitor resistance
title_full Genome-wide and high-density CRISPR-Cas9 screens identify point mutations in PARP1 causing PARP inhibitor resistance
title_fullStr Genome-wide and high-density CRISPR-Cas9 screens identify point mutations in PARP1 causing PARP inhibitor resistance
title_full_unstemmed Genome-wide and high-density CRISPR-Cas9 screens identify point mutations in PARP1 causing PARP inhibitor resistance
title_sort genome-wide and high-density crispr-cas9 screens identify point mutations in parp1 causing parp inhibitor resistance
publisher Nature Portfolio
publishDate 2018
url https://doaj.org/article/1eb977c74fb546b0a7321e49be5d0643
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