Cdt1 stabilizes kinetochore-microtubule attachments via an Aurora B kinase-dependent mechanism

Shivangi Agarwal, Kyle Paul Smith, Yizhuo Zhou, Aussie Suzuki, Richard Mckenney, Dileep Varma

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Robust kinetochore-microtubule (kMT) attachment is critical for accurate chromosome segregation. G2/M-specific depletion of human Cdt1 that localizes to kinetochores in an Ndc80 complex-dependent manner leads to abnormal kMT attachments and mitotic arrest. This indicates an independent mitotic role for Cdt1 in addition to its prototypic function in DNA replication origin licensing. Here, we show that Cdt1 directly binds to microtubules (MTs). Endogenous or transiently expressed Cdt1 localizes to both mitotic spindle MTs and kinetochores. Deletion mapping of Cdt1 revealed that the regions comprising the middle and C-terminal winged-helix domains but lacking the N-terminal unstructured region were required for efficient MT binding. Mitotic kinase Aurora B interacts with and phosphorylates Cdt1. Aurora B-phosphomimetic Cdt1 exhibited attenuated MT binding, and its cellular expression induced defective kMT attachments with a concomitant delay in mitotic progression. Thus we provide mechanistic insight into how Cdt1 affects overall kMT stability in an Aurora B kinase phosphorylation-dependent manner; which is envisioned to augment the MT-binding of the Ndc80 complex.

Original languageEnglish (US)
Pages (from-to)3446-3463
Number of pages18
JournalThe Journal of cell biology
Volume217
Issue number10
DOIs
StatePublished - Oct 1 2018

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Aurora Kinase B
Kinetochores
Microtubules
Chromosome Segregation
Spindle Apparatus
Replication Origin
Licensure
DNA Replication
Phosphorylation

ASJC Scopus subject areas

  • Cell Biology

Cite this

Cdt1 stabilizes kinetochore-microtubule attachments via an Aurora B kinase-dependent mechanism. / Agarwal, Shivangi; Smith, Kyle Paul; Zhou, Yizhuo; Suzuki, Aussie; Mckenney, Richard; Varma, Dileep.

In: The Journal of cell biology, Vol. 217, No. 10, 01.10.2018, p. 3446-3463.

Research output: Contribution to journalArticle

Agarwal, Shivangi ; Smith, Kyle Paul ; Zhou, Yizhuo ; Suzuki, Aussie ; Mckenney, Richard ; Varma, Dileep. / Cdt1 stabilizes kinetochore-microtubule attachments via an Aurora B kinase-dependent mechanism. In: The Journal of cell biology. 2018 ; Vol. 217, No. 10. pp. 3446-3463.
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