DOI: 10.1083/jcb.153.3.517. Merotelic Kinetochore Orientation Is a Major Mechanism of Aneuploidy in Mitotic Mammalian Tissue Cells

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

10.1083/jcb.153.3.517

Crossref journal-article

Rockefeller University Press

The Journal of Cell Biology (291)

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.

Bibliography

Cimini, D., Howell, B., Maddox, P., Khodjakov, A., Degrassi, F., & Salmon, E. D. (2001). Merotelic Kinetochore Orientation Is a Major Mechanism of Aneuploidy in Mitotic Mammalian Tissue Cells. The Journal of Cell Biology, 153(3), 517â528.

Authors 6

Daniela Cimini (first)
Bonnie Howell (additional)
Paul Maddox (additional)
Alexey Khodjakov (additional)
Francesca Degrassi (additional)
E.D. Salmon (additional)

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Dates

Type	When
Created	23 years ago (July 26, 2002, 12:46 p.m.)
Deposited	2 years ago (July 28, 2023, 11:01 p.m.)
Indexed	2 hours, 53 minutes ago (Aug. 26, 2025, 2:41 a.m.)
Issued	24 years, 4 months ago (April 24, 2001)
Published	24 years, 4 months ago (April 24, 2001)
Published Online	24 years, 4 months ago (April 24, 2001)
Published Print	24 years, 3 months ago (April 30, 2001)

Funders 0

None

BibTeX

@article{Cimini_2001, title={Merotelic Kinetochore Orientation Is a Major Mechanism of Aneuploidy in Mitotic Mammalian Tissue Cells}, volume={153}, ISSN={1540-8140}, url={http://dx.doi.org/10.1083/jcb.153.3.517}, DOI={10.1083/jcb.153.3.517}, number={3}, journal={The Journal of Cell Biology}, publisher={Rockefeller University Press}, author={Cimini, Daniela and Howell, Bonnie and Maddox, Paul and Khodjakov, Alexey and Degrassi, Francesca and Salmon, E.D.}, year={2001}, month=apr, pages={517–528} }

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