dc.contributor.author | Barazas, M | |
dc.contributor.author | Annunziato, S | |
dc.contributor.author | Pettitt, SJ | |
dc.contributor.author | de Krijger, I | |
dc.contributor.author | Ghezraoui, H | |
dc.contributor.author | Roobol, SJ | |
dc.contributor.author | Lutz, C | |
dc.contributor.author | Frankum, J | |
dc.contributor.author | Song, FF | |
dc.contributor.author | Brough, R | |
dc.contributor.author | Evers, B | |
dc.contributor.author | Gogola, E | |
dc.contributor.author | Bhin, J | |
dc.contributor.author | van de Ven, M | |
dc.contributor.author | van Gent, DC | |
dc.contributor.author | Jacobs, JJL | |
dc.contributor.author | Chapman, R | |
dc.contributor.author | Lord, CJ | |
dc.contributor.author | Jonkers, J | |
dc.contributor.author | Rottenberg, S | |
dc.date.accessioned | 2018-06-05T08:21:53Z | |
dc.date.issued | 2018-05-15 | |
dc.identifier.citation | Cell reports, 2018, 23 (7), pp. 2107 - 2118 | |
dc.identifier.issn | 2211-1247 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/1701 | |
dc.identifier.eissn | 2211-1247 | |
dc.identifier.doi | 10.1016/j.celrep.2018.04.046 | |
dc.description.abstract | Selective 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.format | Print | |
dc.format.extent | 2107 - 2118 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | CELL PRESS | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Cell Line, Tumor | |
dc.subject | Telomere | |
dc.subject | Animals | |
dc.subject | Mice | |
dc.subject | Disease Models, Animal | |
dc.subject | Multiprotein Complexes | |
dc.subject | BRCA1 Protein | |
dc.subject | Drug Resistance, Neoplasm | |
dc.subject | Female | |
dc.subject | DNA Breaks, Double-Stranded | |
dc.subject | CRISPR-Cas Systems | |
dc.subject | Poly(ADP-ribose) Polymerase Inhibitors | |
dc.subject | Mouse Embryonic Stem Cells | |
dc.title | The CST Complex Mediates End Protection at Double-Strand Breaks and Promotes PARP Inhibitor Sensitivity in BRCA1-Deficient Cells. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2018-04-11 | |
rioxxterms.versionofrecord | 10.1016/j.celrep.2018.04.046 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by-nc-nd/4.0 | |
rioxxterms.licenseref.startdate | 2018-05 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Cell reports | |
pubs.issue | 7 | |
pubs.notes | No 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-status | Published | |
pubs.volume | 23 | |
pubs.embargo.terms | No embargo | |
icr.researchteam | Gene Function | |
dc.contributor.icrauthor | Pettitt, Stephen | |
dc.contributor.icrauthor | Song, Feifei | |
dc.contributor.icrauthor | Lord, Christopher | |