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Centromere-Independent Accumulation of Cohesin at Ectopic Heterochromatin Sites Induces Chromosome Stretching during Anaphase

2014-10-07Journal article Open access
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dc.contributor.authorOliveira, Raquel A.
dc.contributor.authorKotadia, Shaila
dc.contributor.authorTavares, Alexandra
dc.contributor.authorMirkovic, Mihailo
dc.contributor.authorBowlin, Katherine
dc.contributor.authorEichinger, Christian S.
dc.contributor.authorNasmyth, Kim
dc.contributor.authorSullivan, William
dc.date.accessioned2015-10-06T15:05:05Z
dc.date.available2015-10-06T15:05:05Z
dc.date.issued2014-10-07
dc.description.abstractPericentric heterochromatin, while often considered as "junk" DNA, plays important functions in chromosome biology. It contributes to sister chromatid cohesion, a process mediated by the cohesin complex that ensures proper genome segregation during nuclear division. Long stretches of heterochromatin are almost exclusively placed at centromere-proximal regions but it remains unclear if there is functional (or mechanistic) importance in linking the sites of sister chromatid cohesion to the chromosomal regions that mediate spindle attachment (the centromere). Using engineered chromosomes in Drosophila melanogaster, we demonstrate that cohesin enrichment is dictated by the presence of heterochromatin rather than centromere proximity. This preferential accumulation is caused by an enrichment of the cohesin-loading factor (Nipped-B/NIPBL/Scc2) at dense heterochromatic regions. As a result, chromosome translocations containing ectopic pericentric heterochromatin embedded in euchromatin display additional cohesin-dependent constrictions. These ectopic cohesion sites, placed away from the centromere, disjoin abnormally during anaphase and chromosomes exhibit a significant increase in length during anaphase (termed chromatin stretching). These results provide evidence that long stretches of heterochromatin distant from the centromere, as often found in many cancers, are sufficient to induce abnormal accumulation of cohesin at these sites and thereby compromise the fidelity of chromosome segregation.pt_PT
dc.description.sponsorshipMarie Curie Career Integration Grant, European Research Council, National Institutes of Health (GM046409-19), California Institute for Regenerative Medicine (TG2-01157, FA1-00617-1).pt_PT
dc.identifier10.1371/journal.pbio.1001962
dc.identifier.citationOliveira RA, Kotadia S, Tavares A, Mirkovic M, Bowlin K, et al. (2014) Centromere-Independent Accumulation of Cohesin at Ectopic Heterochromatin Sites Induces Chromosome Stretching during Anaphase. PLoS Biol 12(10): e1001962. doi:10.1371/journal.pbio.1001962pt_PT
dc.identifier.doi10.1371/journal.pbio.1001962
dc.identifier.urihttp://hdl.handle.net/10400.7/367
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherPLOSpt_PT
dc.relationChromosome Condensation and Cohesion
dc.relation.publisherversionhttp://www.plosbiology.org/article/Authors/info:doi/10.1371/journal.pbio.1001962pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.titleCentromere-Independent Accumulation of Cohesin at Ectopic Heterochromatin Sites Induces Chromosome Stretching during Anaphasept_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleChromosome Condensation and Cohesion
oaire.awardURIinfo:eu-repo/grantAgreement/EC/FP7/321883/EU
oaire.citation.endPage16pt_PT
oaire.citation.issue10pt_PT
oaire.citation.startPage1pt_PT
oaire.citation.titlePlos Biologypt_PT
oaire.citation.volume12pt_PT
oaire.fundingStreamFP7
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.nameEuropean Commission
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublicationbc69ed99-dc80-4ac2-80f3-0f5a049f116b
relation.isProjectOfPublication.latestForDiscoverybc69ed99-dc80-4ac2-80f3-0f5a049f116b

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