Centromere-independent accumulation of cohesin at ectopic heterochromatin sites induces chromosome stretching during anaphase.

Autor: Oliveira RA; Instituto Gulbenkian de Ciência, Oeiras, Portugal; Department of Biochemistry, University of Oxford, United Kingdom., Kotadia S; Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, Santa Cruz, California., Tavares A; Instituto Gulbenkian de Ciência, Oeiras, Portugal., Mirkovic M; Instituto Gulbenkian de Ciência, Oeiras, Portugal., Bowlin K; Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, Santa Cruz, California., Eichinger CS; Department of Biochemistry, University of Oxford, United Kingdom., Nasmyth K; Department of Biochemistry, University of Oxford, United Kingdom., Sullivan W; Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, Santa Cruz, California.
Jazyk: angličtina
Zdroj: PLoS biology [PLoS Biol] 2014 Oct 07; Vol. 12 (10), pp. e1001962. Date of Electronic Publication: 2014 Oct 07 (Print Publication: 2014).
DOI: 10.1371/journal.pbio.1001962
Abstrakt: Pericentric 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.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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