Publication: Selective Loss of PARG Restores PARylation and Counteracts PARP Inhibitor-Mediated Synthetic Lethality.
cris.virtual.author-orcid | 0000-0003-2044-9844 | |
cris.virtualsource.author-orcid | 3ce5c712-81bb-4245-9893-0aa479809c45 | |
datacite.rights | open.access | |
dc.contributor.author | Gogola, Ewa | |
dc.contributor.author | Duarte, Alexandra A | |
dc.contributor.author | de Ruiter, Julian R | |
dc.contributor.author | Wiegant, Wouter W | |
dc.contributor.author | Schmid, Jonas A | |
dc.contributor.author | de Bruijn, Roebi | |
dc.contributor.author | James, Dominic I | |
dc.contributor.author | Guerrero Llobet, Sergi | |
dc.contributor.author | Vis, Daniel J | |
dc.contributor.author | Annunziato, Stefano | |
dc.contributor.author | van den Broek, Bram | |
dc.contributor.author | Barazas, Marco | |
dc.contributor.author | Kersbergen, Ariena | |
dc.contributor.author | van de Ven, Marieke | |
dc.contributor.author | Tarsounas, Madalena | |
dc.contributor.author | Ogilvie, Donald J | |
dc.contributor.author | van Vugt, Marcel | |
dc.contributor.author | Wessels, Lodewyk F A | |
dc.contributor.author | Bartkova, Jirina | |
dc.contributor.author | Gromova, Irina | |
dc.contributor.author | Andújar-Sánchez, Miguel | |
dc.contributor.author | Bartek, Jiri | |
dc.contributor.author | Lopes, Massimo | |
dc.contributor.author | van Attikum, Haico | |
dc.contributor.author | Borst, Piet | |
dc.contributor.author | Jonkers, Jos | |
dc.contributor.author | Rottenberg, Sven | |
dc.date.accessioned | 2025-01-08T20:33:35Z | |
dc.date.available | 2025-01-08T20:33:35Z | |
dc.date.issued | 2018-06-11 | |
dc.description.abstract | Inhibitors of poly(ADP-ribose) (PAR) polymerase (PARPi) have recently entered the clinic for the treatment of homologous recombination (HR)-deficient cancers. Despite the success of this approach, drug resistance is a clinical hurdle, and we poorly understand how cancer cells escape the deadly effects of PARPi without restoring the HR pathway. By combining genetic screens with multi-omics analysis of matched PARPi-sensitive and -resistant Brca2-mutated mouse mammary tumors, we identified loss of PAR glycohydrolase (PARG) as a major resistance mechanism. We also found the presence of PARG-negative clones in a subset of human serous ovarian and triple-negative breast cancers. PARG depletion restores PAR formation and partially rescues PARP1 signaling. Importantly, PARG inactivation exposes vulnerabilities that can be exploited therapeutically. | |
dc.description.numberOfPages | 16 | |
dc.description.sponsorship | Institut für Tierpathologie (ITPA) | |
dc.identifier.doi | 10.7892/boris.122087 | |
dc.identifier.pmid | 29894693 | |
dc.identifier.publisherDOI | 10.1016/j.ccell.2018.05.008 | |
dc.identifier.uri | https://boris-portal.unibe.ch/handle/20.500.12422/200300 | |
dc.language.iso | en | |
dc.publisher | Cell Press | |
dc.relation.ispartof | Cancer cell | |
dc.relation.issn | 1535-6108 | |
dc.relation.organization | DCD5A442C208E17DE0405C82790C4DE2 | |
dc.relation.organization | DCD5A442C072E17DE0405C82790C4DE2 | |
dc.relation.organization | DCD5A442C1CCE17DE0405C82790C4DE2 | |
dc.subject | BRCA1 BRCA2 PARG PARP inhibitor PARP1 PARylation drug resistance homologous recombination replication fork | |
dc.subject.ddc | 500 - Science::570 - Life sciences; biology | |
dc.subject.ddc | 600 - Technology::610 - Medicine & health | |
dc.subject.ddc | 600 - Technology::630 - Agriculture | |
dc.title | Selective Loss of PARG Restores PARylation and Counteracts PARP Inhibitor-Mediated Synthetic Lethality. | |
dc.type | article | |
dspace.entity.type | Publication | |
dspace.file.type | text | |
dspace.file.type | text | |
oaire.citation.endPage | 1093.e12 | |
oaire.citation.issue | 6 | |
oaire.citation.startPage | 1078 | |
oaire.citation.volume | 33 | |
oairecerif.author.affiliation | Institut für Tierpathologie (ITPA) | |
unibe.contributor.role | creator | |
unibe.contributor.role | creator | |
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unibe.contributor.role | creator | |
unibe.contributor.role | creator | |
unibe.date.embargoChanged | 2019-07-01 00:33:04 | |
unibe.date.licenseChanged | 2019-10-24 08:36:12 | |
unibe.description.ispublished | pub | |
unibe.eprints.legacyId | 122087 | |
unibe.journal.abbrevTitle | CANCER CELL | |
unibe.refereed | true | |
unibe.subtype.article | journal |
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