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Cdk Activity Couples Epigenetic Centromere Inheritance to Cell Cycle Progression

2012-01-17Journal article Open access
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dc.contributor.authorSilva, Mariana C.C.
dc.contributor.authorBodor, Dani L.
dc.contributor.authorStellfox, Madison E.
dc.contributor.authorMartins, Nuno M.C.
dc.contributor.authorHochegger, Helfrid
dc.contributor.authorFoltz, Daniel R.
dc.contributor.authorJansen, Lars E.T.
dc.date.accessioned2016-05-24T11:34:42Z
dc.date.available2016-05-24T11:34:42Z
dc.date.issued2012-01-17
dc.description.abstractCentromeres form the site of chromosome attachment to microtubules during mitosis. Identity of these loci is maintained epigenetically by nucleosomes containing the histone H3 variant CENP-A. Propagation of CENP-A chromatin is uncoupled from DNA replication initiating only during mitotic exit. We now demonstrate that inhibition of Cdk1 and Cdk2 activities is sufficient to trigger CENP-A assembly throughout the cell cycle in a manner dependent on the canonical CENP-A assembly machinery. We further show that the key CENP-A assembly factor Mis18BP1(HsKNL2) is phosphorylated in a cell cycle-dependent manner that controls its centromere localization during mitotic exit. These results strongly support a model in which the CENP-A assembly machinery is poised for activation throughout the cell cycle but kept in an inactive noncentromeric state by Cdk activity during S, G2, and M phases. Alleviation of this inhibition in G1 phase ensures tight coupling between DNA replication, cell division, and subsequent centromere maturation.pt_PT
dc.description.sponsorshipFCT doctoral fellowship: (SFRH/BD/33219/2007); FCT grant: (BIA-BCM/100557/2008); Fundação Calouste Gulbenkian; European Commission FP7 programme; EMBO installation grant.pt_PT
dc.identifier.citationMariana C.C. Silva, Dani L. Bodor, Madison E. Stellfox, Nuno M.C. Martins, Helfrid Hochegger, Daniel R. Foltz, Lars E.T. Jansen, Cdk Activity Couples Epigenetic Centromere Inheritance to Cell Cycle Progression, Developmental Cell, Volume 22, Issue 1, 17 January 2012, Pages 52-63, ISSN 1534-5807, http://dx.doi.org/10.1016/j.devcel.2011.10.014.pt_PT
dc.identifier.doi10.1016/j.devcel.2011.10.014pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.7/616
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherCell Presspt_PT
dc.relation.publisherversionhttp://www.sciencedirect.com/science/article/pii/S1534580711004667pt_PT
dc.subjectAutoantigenspt_PT
dc.subjectBlotting, Westernpt_PT
dc.subjectCDC2 Protein Kinasept_PT
dc.subjectCell Cyclept_PT
dc.subjectCell Divisionpt_PT
dc.subjectCentromerept_PT
dc.subjectChromatinpt_PT
dc.subjectChromosomal Proteins, Non-Histonept_PT
dc.subjectCyclin-Dependent Kinase 2pt_PT
dc.subjectFlow Cytometrypt_PT
dc.subjectFluorescent Antibody Techniquept_PT
dc.subjectG1 Phasept_PT
dc.subjectHeLa Cellspt_PT
dc.subjectHumanspt_PT
dc.subjectMitosispt_PT
dc.subjectPhosphorylationpt_PT
dc.subjectEpigenomicspt_PT
dc.titleCdk Activity Couples Epigenetic Centromere Inheritance to Cell Cycle Progressionpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage63pt_PT
oaire.citation.issue1pt_PT
oaire.citation.startPage52pt_PT
oaire.citation.titleDevelopmental Cellpt_PT
oaire.citation.volume22pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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