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dc.contributor.authorBarazas, M
dc.contributor.authorAnnunziato, S
dc.contributor.authorPettitt, SJ
dc.contributor.authorde Krijger, I
dc.contributor.authorGhezraoui, H
dc.contributor.authorRoobol, SJ
dc.contributor.authorLutz, C
dc.contributor.authorFrankum, J
dc.contributor.authorSong, FF
dc.contributor.authorBrough, R
dc.contributor.authorEvers, B
dc.contributor.authorGogola, E
dc.contributor.authorBhin, J
dc.contributor.authorvan de Ven, M
dc.contributor.authorvan Gent, DC
dc.contributor.authorJacobs, JJL
dc.contributor.authorChapman, R
dc.contributor.authorLord, CJ
dc.contributor.authorJonkers, J
dc.contributor.authorRottenberg, S
dc.date.accessioned2018-06-05T08:21:53Z
dc.date.issued2018-05
dc.identifier.citationCell reports, 2018, 23 (7), pp. 2107 - 2118
dc.identifier.issn2211-1247
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1701
dc.identifier.eissn2211-1247
dc.identifier.doi10.1016/j.celrep.2018.04.046
dc.description.abstractSelective elimination of BRCA1-deficient cells by inhibitors of poly(ADP-ribose) polymerase (PARP) is a prime example of the concept of synthetic lethality in cancer therapy. This interaction is counteracted by the restoration of BRCA1-independent homologous recombination through loss of factors such as 53BP1, RIF1, and REV7/MAD2L2, which inhibit end resection of DNA double-strand breaks (DSBs). To identify additional factors involved in this process, we performed CRISPR/SpCas9-based loss-of-function screens and selected for factors that confer PARP inhibitor (PARPi) resistance in BRCA1-deficient cells. Loss of members of the CTC1-STN1-TEN1 (CST) complex were found to cause PARPi resistance in BRCA1-deficient cells in vitro and in vivo. We show that CTC1 depletion results in the restoration of end resection and that the CST complex may act downstream of 53BP1/RIF1. These data suggest that, in addition to its role in protecting telomeres, the CST complex also contributes to protecting DSBs from end resection.
dc.formatPrint
dc.format.extent2107 - 2118
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectCell Line, Tumor
dc.subjectTelomere
dc.subjectAnimals
dc.subjectMice
dc.subjectDisease Models, Animal
dc.subjectMultiprotein Complexes
dc.subjectBRCA1 Protein
dc.subjectDrug Resistance, Neoplasm
dc.subjectFemale
dc.subjectDNA Breaks, Double-Stranded
dc.subjectCRISPR-Cas Systems
dc.subjectPoly(ADP-ribose) Polymerase Inhibitors
dc.subjectMouse Embryonic Stem Cells
dc.titleThe CST Complex Mediates End Protection at Double-Strand Breaks and Promotes PARP Inhibitor Sensitivity in BRCA1-Deficient Cells.
dc.typeJournal Article
dcterms.dateAccepted2018-04-11
rioxxterms.versionofrecord10.1016/j.celrep.2018.04.046
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by-nc-nd/4.0
rioxxterms.licenseref.startdate2018-05
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfCell reports
pubs.issue7
pubs.notesNo embargo
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Gene Function
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Gene Function
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Gene Function
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Gene Function
pubs.publication-statusPublished
pubs.volume23en_US
pubs.embargo.termsNo embargo
icr.researchteamGene Functionen_US
dc.contributor.icrauthorSong, Feifeien
dc.contributor.icrauthorLord, Christopheren
dc.contributor.icrauthorPettitt, Stephenen


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