Centromere mechanical maturation during mammalian cell mitosis

Lauren A. Harasymiw, Damien Tank, Mark McClellan, Neha Panigrahy, Melissa K Gardner

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

During mitosis, tension develops across the centromere as a result of spindle-based forces. Metaphase tension may be critical in preventing mitotic chromosome segregation errors, however, the nature of force transmission at the centromere and the role of centromere mechanics in controlling metaphase tension remains unknown. We combined quantitative, biophysical microscopy with computational analysis to elucidate the mechanics of the centromere in unperturbed, mitotic human cells. We discovered that the mechanical stiffness of the human centromere matures during mitotic progression, which leads to amplified centromere tension specifically at metaphase. Centromere mechanical maturation is disrupted across multiple aneuploid cell lines, leading to a weak metaphase tension signal. Further, increasing deficiencies in centromere mechanical maturation are correlated with rising frequencies of lagging, merotelic chromosomes in anaphase, leading to segregation defects at telophase. Thus, we reveal a centromere maturation process that may be critical to the fidelity of chromosome segregation during mitosis.

Original languageEnglish (US)
Article number1761
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

Fingerprint

mitosis
Centromere
Chromosomes
Mitosis
Cells
chromosomes
Mechanics
Metaphase
Chromosome Segregation
Microscopic examination
Stiffness
spindles
Defects
cultured cells
progressions
stiffness
Telophase
Anaphase
microscopy
Aneuploidy

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

Cite this

Centromere mechanical maturation during mammalian cell mitosis. / Harasymiw, Lauren A.; Tank, Damien; McClellan, Mark; Panigrahy, Neha; Gardner, Melissa K.

In: Nature communications, Vol. 10, No. 1, 1761, 01.12.2019.

Research output: Contribution to journalArticle

Harasymiw, Lauren A. ; Tank, Damien ; McClellan, Mark ; Panigrahy, Neha ; Gardner, Melissa K. / Centromere mechanical maturation during mammalian cell mitosis. In: Nature communications. 2019 ; Vol. 10, No. 1.
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