Identification of regulators of poly-ADP-ribose polymerase inhibitor response through complementary CRISPR knockout and activation screens

Mutations in the homologous recombination proteins BRCA1 and BRCA2 can sensitize cells to treatment with inhibitors of poly-ADP-ribose polymerase 1 (PARPi), but resistance to the treatment can occur. Here the authors by genome-wide CRISPR knockout and activation screens reveal novel pathways of PARP...

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Main Authors: Kristen E. Clements, Emily M. Schleicher, Tanay Thakar, Anastasia Hale, Ashna Dhoonmoon, Nathanial J. Tolman, Anchal Sharma, Xinwen Liang, Yuka Imamura Kawasawa, Claudia M. Nicolae, Hong-Gang Wang, Subhajyoti De, George-Lucian Moldovan
Format: Article
Language:English
Published: Nature Publishing Group 2020-11-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-020-19961-w
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spelling doaj-bbee1b004cdc4bdebae2ddc9b6d5a3f32021-05-11T08:43:34ZengNature Publishing GroupNature Communications2041-17232020-11-0111111410.1038/s41467-020-19961-wIdentification of regulators of poly-ADP-ribose polymerase inhibitor response through complementary CRISPR knockout and activation screensKristen E. Clements0Emily M. Schleicher1Tanay Thakar2Anastasia Hale3Ashna Dhoonmoon4Nathanial J. Tolman5Anchal Sharma6Xinwen Liang7Yuka Imamura Kawasawa8Claudia M. Nicolae9Hong-Gang Wang10Subhajyoti De11George-Lucian Moldovan12Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of MedicineDepartment of Biochemistry and Molecular Biology, The Pennsylvania State University College of MedicineDepartment of Biochemistry and Molecular Biology, The Pennsylvania State University College of MedicineDepartment of Biochemistry and Molecular Biology, The Pennsylvania State University College of MedicineDepartment of Biochemistry and Molecular Biology, The Pennsylvania State University College of MedicineDepartment of Biochemistry and Molecular Biology, The Pennsylvania State University College of MedicineRutgers Cancer Institute of New Jersey, Rutgers the State University of New JerseyDepartment of Pediatrics, The Pennsylvania State University College of MedicineDepartment of Biochemistry and Molecular Biology, The Pennsylvania State University College of MedicineDepartment of Biochemistry and Molecular Biology, The Pennsylvania State University College of MedicineDepartment of Pediatrics, The Pennsylvania State University College of MedicineRutgers Cancer Institute of New Jersey, Rutgers the State University of New JerseyDepartment of Biochemistry and Molecular Biology, The Pennsylvania State University College of MedicineMutations in the homologous recombination proteins BRCA1 and BRCA2 can sensitize cells to treatment with inhibitors of poly-ADP-ribose polymerase 1 (PARPi), but resistance to the treatment can occur. Here the authors by genome-wide CRISPR knockout and activation screens reveal novel pathways of PARPi resistance in BRCA2-deficient cells.https://doi.org/10.1038/s41467-020-19961-w
collection DOAJ
language English
format Article
sources DOAJ
author Kristen E. Clements
Emily M. Schleicher
Tanay Thakar
Anastasia Hale
Ashna Dhoonmoon
Nathanial J. Tolman
Anchal Sharma
Xinwen Liang
Yuka Imamura Kawasawa
Claudia M. Nicolae
Hong-Gang Wang
Subhajyoti De
George-Lucian Moldovan
spellingShingle Kristen E. Clements
Emily M. Schleicher
Tanay Thakar
Anastasia Hale
Ashna Dhoonmoon
Nathanial J. Tolman
Anchal Sharma
Xinwen Liang
Yuka Imamura Kawasawa
Claudia M. Nicolae
Hong-Gang Wang
Subhajyoti De
George-Lucian Moldovan
Identification of regulators of poly-ADP-ribose polymerase inhibitor response through complementary CRISPR knockout and activation screens
Nature Communications
author_facet Kristen E. Clements
Emily M. Schleicher
Tanay Thakar
Anastasia Hale
Ashna Dhoonmoon
Nathanial J. Tolman
Anchal Sharma
Xinwen Liang
Yuka Imamura Kawasawa
Claudia M. Nicolae
Hong-Gang Wang
Subhajyoti De
George-Lucian Moldovan
author_sort Kristen E. Clements
title Identification of regulators of poly-ADP-ribose polymerase inhibitor response through complementary CRISPR knockout and activation screens
title_short Identification of regulators of poly-ADP-ribose polymerase inhibitor response through complementary CRISPR knockout and activation screens
title_full Identification of regulators of poly-ADP-ribose polymerase inhibitor response through complementary CRISPR knockout and activation screens
title_fullStr Identification of regulators of poly-ADP-ribose polymerase inhibitor response through complementary CRISPR knockout and activation screens
title_full_unstemmed Identification of regulators of poly-ADP-ribose polymerase inhibitor response through complementary CRISPR knockout and activation screens
title_sort identification of regulators of poly-adp-ribose polymerase inhibitor response through complementary crispr knockout and activation screens
publisher Nature Publishing Group
series Nature Communications
issn 2041-1723
publishDate 2020-11-01
description Mutations in the homologous recombination proteins BRCA1 and BRCA2 can sensitize cells to treatment with inhibitors of poly-ADP-ribose polymerase 1 (PARPi), but resistance to the treatment can occur. Here the authors by genome-wide CRISPR knockout and activation screens reveal novel pathways of PARPi resistance in BRCA2-deficient cells.
url https://doi.org/10.1038/s41467-020-19961-w
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