ArticlePloS one2011
Uncoordinated loss of chromatid cohesion is a common outcome of extended metaphase arrest.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 87 citations in OpenAlex.
- Yeast with elevated chromosome numbers are addicted to high levels of Mps1.bioRxiv : the preprint server for biology · 2025Article
- Exploiting a living biobank to delineate mechanisms underlying disease-specific chromosome instability.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2023Review
- Tetraploidy-linked sensitization to CENP-E inhibition in human cells.Molecular oncology · 2023Article
- Phosphorylation and Pin1 binding to the LIC1 subunit selectively regulate mitotic dynein functions.The Journal of cell biology · 2021Article
- The Hec1/Ndc80 tail domain is required for force generation at kinetochores, but is dispensable for kinetochore-microtubule attachment formation and Ska complex recruitment.Molecular biology of the cell · 2020Article
- CSAG1 maintains the integrity of the mitotic centrosome in cells with defective p53.Journal of cell science · 2020Article
- A living biobank of ovarian cancer ex vivo models reveals profound mitotic heterogeneity.Nature communications · 2020Article
- Non-redundant roles in sister chromatid cohesion of the DNA helicase DDX11 and the SMC3 acetyl transferases ESCO1 and ESCO2.PloS one · 2020Article
- Meiotic Kinetochores Fragment into Multiple Lobes upon Cohesin Loss in Aging Eggs.Current biology : CB · 2019Article
- Aurora B kinase activity-dependent and -independent functions of the chromosomal passenger complex in regulating sister chromatid cohesion.The Journal of biological chemistry · 2019Article
- A positive feedback mechanism ensures proper assembly of the functional inner centromere during mitosis in human cells.The Journal of biological chemistry · 2019Article
- Aurora A Protein Kinase: To the Centrosome and Beyond.Biomolecules · 2019Review
- Multiple determinants and consequences of cohesion fatigue in mammalian cells.Molecular biology of the cell · 2018Article
- Non-random Mis-segregation of Human Chromosomes.Cell reports · 2018Article
- Aurora A-dependent CENP-A phosphorylation at inner centromeres protects bioriented chromosomes against cohesion fatigue.Nature communications · 2018Article
- PARP inhibition causes premature loss of cohesion in cancer cells.Oncotarget · 2017Article
- Phosphatase-regulated recruitment of the spindle- and kinetochore-associated (Ska) complex to kinetochores.Biology open · 2017Article
- Esco1 and Esco2 regulate distinct cohesin functions during cell cycle progression.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Mechanisms of Chromosome Congression during Mitosis.Biology · 2017Review
- Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Chromosome segregation requires coordinated separation of sister chromatids following biorientation of all chromosomes on the mitotic spindle. Chromatid separation at the metaphase-to-anaphase transition is accomplished by cleavage of the cohesin complex that holds chromatids together. Here we show using live-cell imaging that extending the metaphase bioriented state using five independent perturbations (expression of non-degradable Cyclin B, expression of a Spindly point mutant that prevents spindle checkpoint silencing, depletion of the anaphase inducer Cdc20, treatment with a proteasome inhibitor, or treatment with an inhibitor of the mitotic kinesin CENP-E) leads to eventual scattering of chromosomes on the spindle. This scattering phenotype is characterized by uncoordinated loss of cohesion between some, but not all sister chromatids and subsequent spindle defects that include centriole separation. Cells with scattered chromosomes persist long-term in a mitotic state and eventually die or exit. Partial cohesion loss-associated scattering is observed in both transformed cells and in karyotypically normal human cells, albeit at lower penetrance. Suppressing microtubule dynamics reduces scattering, suggesting that cohesion at centromeres is unable to resist dynamic microtubule-dependent pulling forces on the kinetochores. Consistent with this view, strengthening cohesion by inhibiting the two pathways responsible for its removal significantly inhibits scattering. These results establish that chromosome scattering due to uncoordinated partial loss of chromatid cohesion is a common outcome following extended arrest with bioriented chromosomes in human cells. These findings have important implications for analysis of mitotic phenotypes in human cells and for development of anti-mitotic chemotherapeutic approaches in the treatment of cancer.
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