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PLK1 facilitates chromosome biorientation by suppressing centromere disintegration driven by BLM-mediated unwinding and spindle pulling

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  • Owen Addis Jones

    (University of Sussex)

  • Ankana Tiwari

    (University of Sussex)

  • Tomisin Olukoga

    (University of Sussex)

  • Alex Herbert

    (University of Sussex)

  • Kok-Lung Chan

    (University of Sussex)

Abstract

Centromeres provide a pivotal function for faithful chromosome segregation. They serve as a foundation for the assembly of the kinetochore complex and spindle connection, which is essential for chromosome biorientation. Cells lacking Polo-like kinase 1 (PLK1) activity suffer severe chromosome alignment defects, which is believed primarily due to unstable kinetochore-microtubule attachment. Here, we reveal a previously undescribed mechanism named ‘centromere disintegration’ that drives chromosome misalignment in PLK1-inactivated cells. We find that PLK1 inhibition does not necessarily compromise metaphase establishment, but instead its maintenance. We demonstrate that this is caused by unlawful unwinding of DNA by BLM helicase at a specific centromere domain underneath kinetochores. Under bipolar spindle pulling, the distorted centromeres are promptly decompacted into DNA threadlike molecules, leading to centromere rupture and whole-chromosome arm splitting. Consequently, chromosome alignment collapses. Our study unveils an unexpected role of PLK1 as a chromosome guardian to maintain centromere integrity for chromosome biorientation.

Suggested Citation

  • Owen Addis Jones & Ankana Tiwari & Tomisin Olukoga & Alex Herbert & Kok-Lung Chan, 2019. "PLK1 facilitates chromosome biorientation by suppressing centromere disintegration driven by BLM-mediated unwinding and spindle pulling," Nature Communications, Nature, vol. 10(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10938-y
    DOI: 10.1038/s41467-019-10938-y
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    Cited by:

    1. Poonam Roshan & Sahiti Kuppa & Jenna R. Mattice & Vikas Kaushik & Rahul Chadda & Nilisha Pokhrel & Brunda R. Tumala & Aparna Biswas & Brian Bothner & Edwin Antony & Sofia Origanti, 2023. "An Aurora B-RPA signaling axis secures chromosome segregation fidelity," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    2. Christopher B. Nelson & Samuel Rogers & Kaushik Roychoudhury & Yaw Sing Tan & Caroline J. Atkinson & Alexander P. Sobinoff & Christopher G. Tomlinson & Anton Hsu & Robert Lu & Eloise Dray & Michelle H, 2024. "The Eyes Absent family members EYA4 and EYA1 promote PLK1 activation and successful mitosis through tyrosine dephosphorylation," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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