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Developmental and cancer-associated plasticity of DNA replication preferentially targets GC-poor, lowly expressed and late-replicating regions

hal.structure.identifierInstitut de biologie de l'ENS Paris [IBENS]
dc.contributor.authorWU, Xia
hal.structure.identifierLaboratoire de Physique de l'ENS Lyon [Phys-ENS]
dc.contributor.authorKABALANE, Hadi
hal.structure.identifierInstitut de biologie de l'ENS Paris [IBENS]
dc.contributor.authorKAHLI, Malik
hal.structure.identifierInstitut de biologie de l'ENS Paris [IBENS]
dc.contributor.authorPETRYK, Nataliya
hal.structure.identifierLaboratoire de Physique de l'ENS Lyon [Phys-ENS]
dc.contributor.authorLAPERROUSAZ, Bastien
hal.structure.identifierInstitut de biologie de l'ENS Paris [IBENS]
dc.contributor.authorJASZCZYSZYN, Yan
hal.structure.identifierLaboratoire de Physique de l'ENS Lyon [Phys-ENS]
dc.contributor.authorDRILLON, Guénola
hal.structure.identifierCentre de Recherche en Cancérologie de Lyon [UNICANCER/CRCL]
dc.contributor.authorNICOLINI, Frank-Emmanuel
hal.structure.identifierActions for OnCogenesis understanding and Target Identification in ONcology [ACTION]
dc.contributor.authorPÉROT, Gaëlle
hal.structure.identifierSignalisation, noyaux et innovations en cancérologie [UMR8126]
dc.contributor.authorROBERT, Aude
hal.structure.identifierInstitut de biologie de l'ENS Paris [IBENS]
hal.structure.identifierGenomiqueENS [Genomique ENS]
dc.contributor.authorFUND, Cédric
hal.structure.identifierCentre de Recherches en Cancérologie de Toulouse [CRCT]
hal.structure.identifierInstitut Bergonié [Bordeaux]
dc.contributor.authorCHIBON, Frédéric
dc.contributor.authorXIA, Ruohong
hal.structure.identifierSignalisation, noyaux et innovations en cancérologie [UMR8126]
dc.contributor.authorWIELS, Joëlle
hal.structure.identifierLaboratoire Ondes et Matière d'Aquitaine [LOMA]
hal.structure.identifierLaboratoire de Physique de l'ENS Lyon [Phys-ENS]
dc.contributor.authorARGOUL, Françoise
hal.structure.identifierCentre de Recherche en Cancérologie de Lyon [UNICANCER/CRCL]
dc.contributor.authorMAGUER-SATTA, Véronique
hal.structure.identifierLaboratoire Ondes et Matière d'Aquitaine [LOMA]
hal.structure.identifierLaboratoire de Physique de l'ENS Lyon [Phys-ENS]
dc.contributor.authorARNEODO, Alain
hal.structure.identifierLaboratoire de Physique de l'ENS Lyon [Phys-ENS]
dc.contributor.authorAUDIT, Benjamin
hal.structure.identifierInstitut de biologie de l'ENS Paris [IBENS]
dc.contributor.authorHYRIEN, Olivier
dc.date.issued2018
dc.identifier.issn0305-1048
dc.description.abstractEnThe spatiotemporal program of metazoan DNA repli-cation is regulated during development and altered in cancers. We have generated novel OK-seq, Repli-seq and RNA-seq data to compare the DNA replica-tion and gene expression programs of twelve cancer and non-cancer human cell types. Changes in replication fork directionality (RFD) determined by OK-seq are widespread but more frequent within GC-poor isochores and largely disconnected from transcription changes. Cancer cell RFD profiles cluster with non-cancer cells of similar developmental origin but not with different cancer types. Importantly, recurrent RFD changes are detected in specific tumour progression pathways. Using a model for establishment and early progression of chronic myeloid leukemia (CML), we identify 1027 replication initiation zones (IZs) that progressively change efficiency during long-term expression of the BCR-ABL1 onco-gene, being twice more often downregulated than upregulated. Prolonged expression of BCR-ABL1 results in targeting of new IZs and accentuation of previous efficiency changes. Targeted IZs are predominantly located in GC-poor, late replicating gene deserts and frequently silenced in late CML. Prolonged expression of BCR-ABL1 results in massive deletion of GC-poor, late replicating DNA sequences enriched in origin silencing events. We conclude that BCR-ABL1 expression progressively affects replica-tion and stability of GC-poor, late-replicating regions during CML progression.
dc.description.sponsorshipParis Sciences et Lettres
dc.language.isoen
dc.publisherOxford University Press
dc.title.enDevelopmental and cancer-associated plasticity of DNA replication preferentially targets GC-poor, lowly expressed and late-replicating regions
dc.typeArticle de revue
dc.identifier.doi10.1093/nar/gky797
dc.subject.halSciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire/Génomique, Transcriptomique et Protéomique [q-bio.GN]
bordeaux.journalNucleic Acids Research
bordeaux.page10157–10172
bordeaux.volume46
bordeaux.issue19
bordeaux.peerReviewedoui
hal.identifierhal-02363281
hal.version2
hal.popularnon
hal.audienceInternationale
hal.origin.linkhttps://hal.archives-ouvertes.fr//hal-02363281v2
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