Open Close
Reference
Citation
Oliveira, R.A., Kotadia, S., Tavares, A., Mirkovic, M., Bowlin, K., Eichinger, C.S., Nasmyth, K., Sullivan, W. (2014). Centromere-Independent Accumulation of Cohesin at Ectopic Heterochromatin Sites Induces Chromosome Stretching during Anaphase.  PLoS Biol. 12(10): e1001962.
FlyBase ID
FBrf0226421
Publication Type
Research paper
Abstract

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.

PubMed ID
PubMed Central ID
PMC4188515 (PMC) (EuropePMC)
Associated Information
Comments
Associated Files
Other Information
Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    PLoS Biol.
    Title
    PLoS Biology
    Publication Year
    2003-
    ISBN/ISSN
    1545-7885 1544-9173
    Data From Reference
    Aberrations (3)
    Alleles (7)
    Genes (8)
    Natural transposons (1)
    Experimental Tools (2)
    Transgenic Constructs (5)