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dc.contributor.authorBianco, JN
dc.contributor.authorBergoglio, V
dc.contributor.authorLin, Y-L
dc.contributor.authorPillaire, M-J
dc.contributor.authorSchmitz, A-L
dc.contributor.authorGilhodes, J
dc.contributor.authorLusque, A
dc.contributor.authorMazières, J
dc.contributor.authorLacroix-Triki, M
dc.contributor.authorRoumeliotis, TI
dc.contributor.authorChoudhary, J
dc.contributor.authorMoreaux, J
dc.contributor.authorHoffmann, J-S
dc.contributor.authorTourrière, H
dc.contributor.authorPasero, P
dc.date.accessioned2020-06-11T09:24:56Z
dc.date.issued2019-02-22
dc.identifier.citationNature communications, 2019, 10 (1), pp. 910 - ?
dc.identifier.issn2041-1723
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3719
dc.identifier.eissn2041-1723
dc.identifier.doi10.1038/s41467-019-08886-8
dc.description.abstractOncogene-induced replication stress (RS) promotes cancer development but also impedes tumor growth by activating anti-cancer barriers. To determine how cancer cells adapt to RS, we have monitored the expression of different components of the ATR-CHK1 pathway in primary tumor samples. We show that unlike upstream components of the pathway, the checkpoint mediators Claspin and Timeless are overexpressed in a coordinated manner. Remarkably, reducing the levels of Claspin and Timeless in HCT116 cells to pretumoral levels impeded fork progression without affecting checkpoint signaling. These data indicate that high level of Claspin and Timeless increase RS tolerance by protecting replication forks in cancer cells. Moreover, we report that primary fibroblasts adapt to oncogene-induced RS by spontaneously overexpressing Claspin and Timeless, independently of ATR signaling. Altogether, these data indicate that enhanced levels of Claspin and Timeless represent a gain of function that protects cancer cells from of oncogene-induced RS in a checkpoint-independent manner.
dc.formatElectronic
dc.format.extent910 - ?
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectCell Line, Tumor
dc.subjectHCT116 Cells
dc.subjectHela Cells
dc.subjectHumans
dc.subjectBreast Neoplasms
dc.subjectColorectal Neoplasms
dc.subjectDNA Damage
dc.subjectGenomic Instability
dc.subjectIntracellular Signaling Peptides and Proteins
dc.subjectAdaptor Proteins, Signal Transducing
dc.subjectCell Cycle Proteins
dc.subjectStress, Physiological
dc.subjectMCF-7 Cells
dc.subjectAtaxia Telangiectasia Mutated Proteins
dc.subjectCheckpoint Kinase 1
dc.subjectAdenocarcinoma of Lung
dc.titleOverexpression of Claspin and Timeless protects cancer cells from replication stress in a checkpoint-independent manner.
dc.typeJournal Article
dcterms.dateAccepted2019-02-05
rioxxterms.versionofrecord10.1038/s41467-019-08886-8
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2019-02-22
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfNature communications
pubs.issue1
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR
pubs.publication-statusPublished
pubs.volume10
pubs.embargo.termsNot known
dc.contributor.icrauthorChoudhary, Jyotien


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