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Cited by 568Microtubule and mitosis dynamicsDNA Repair MechanismsGenomics and Chromatin Dynamics

Merotelic Kinetochore Orientation Is a Major Mechanism of Aneuploidy in Mitotic Mammalian Tissue Cells

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Cimini, Daniela, Howell, Bonnie, Maddox, Paul, Khodjakov, Alexey, Degrassi, Francesca, Salmon, E.D.·2001·The Journal of Cell Biology
DOI 10.1083/jcb.153.3.517PMC PMC2190575
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Abstract

In mitotic cells, an error in chromosome segregation occurs when a chromosome is left near the spindle equator after anaphase onset (lagging chromosome). In PtK1 cells, we found 1.16% of untreated anaphase cells exhibiting lagging chromosomes at the spindle equator, and this percentage was enhanced to 17.55% after a mitotic block with 2 μM nocodazole. A lagging chromosome seen during anaphase in control or nocodazole-treated cells was found by confocal immunofluorescence microscopy to be a single chromatid with its kinetochore attached to kinetochore microtubule bundles extending toward opposite poles. This merotelic orientation was verified by electron microscopy. The single kinetochores of lagging chromosomes in anaphase were stretched laterally (1.2–5.6-fold) in the directions of their kinetochore microtubules, indicating that they were not able to achieve anaphase poleward movement because of pulling forces toward opposite poles. They also had inactivated mitotic spindle checkpoint activities since they did not label with either Mad2 or 3F3/2 antibodies. Thus, for mammalian cultured cells, kinetochore merotelic orientation is a major mechanism of aneuploidy not detected by the mitotic spindle checkpoint. The expanded and curved crescent morphology exhibited by kinetochores during nocodazole treatment may promote the high incidence of kinetochore merotelic orientation that occurs after nocodazole washout.

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  • Chromosomally unstable cells exhibit evidence of chromosome missegregation during anaphase.

    “Chromosomally unstable cells exhibit evidence of chromosome missegregation during anaphase3,4”

    From Chromosomal instability drives metastasis through a cytosolic DNA response (2018) · cites this paper as [4]

    The Results section reports lagging chromosomes and occasional sister-chromatid missegregation during anaphase in PtK1 cells. It does not establish that the cells studied were chromosomally unstable, so the claim’s population qualifier is not supported by this paper. (LLM, conf=0.84)

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Cites

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Authors
Cimini, D., Howell, B., Maddox, P., Khodjakov, A., Degrassi, F., & Salmon, E. D.
Affiliations
  • University of North Carolina at Chapel Hill (US)
  • New York State Department of Health (US)
  • Sapienza University of Rome (IT)
ORCID
Venue
The Journal of Cell Biology
Publisher
Rockefeller University Press
Published
2001-04-24
Volume
153
Issue
3
Pages
517-528
ISSN
  • 0021-9525 (ISSN-L)
  • 1540-8140
DOI
10.1083/jcb.153.3.517
PMC
PMC2190575
OpenAlex
W2102960342
Cited by
568
References
1
Citations by year
2026: 17 · 2025: 15 · 2024: 27 · 2023: 36 · 2022: 22 · 2021: 31 · 2020: 21 · 2019: 24 · 2018: 30 · 2017: 24 · 2016: 21 · 2015: 30 · 2014: 24 · 2013: 19 · 2012: 35
FWCI
6.47
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • The Journal of Cell Biology (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
  • UNC Libraries
Funders
  • National Institutes of Health (1s10rr012019-01)
  • National Institute of General Medical Sciences (R37GM024364, R01GM059363, GM59363, R01GM024364)
  • National Center for Research Resources (RR012019)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
aneuploidy, lagging chromosomes, chromosome segregation errors, mitotic spindle checkpoint, kinetochore microtubules, nocodazole, Mad2, PtK1 cells, anaphase
MeSH terms
Anaphase, Aneuploidy, Animals, Epitopes, Calcium-Binding Proteins, Carrier Proteins, Centromere, Chromatids, Chromosomes, Fungal Proteins, Microtubules, Mitosis, Spindle Apparatus, Models, Genetic, Models, Structural, Movement, Nuclear Proteins, Telophase, Nocodazole, Cell Polarity, Kinetochores, Cell Cycle Proteins

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