s41467-019-10938-y.pdf (13.97 MB)
PLK1 facilitates chromosome biorientation by suppressing centromere disintegration driven by BLM-mediated unwinding and spindle pulling
Version 2 2023-06-12, 09:09
Version 1 2023-06-09, 18:11
journal contribution
posted on 2023-06-12, 09:09 authored by Owen Addis, Ankana Tiwari, Tomisin Olukoga, Alex Herbert, Kok-Lung ChanKok-Lung ChanCentromeres 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.
Funding
Molecular basis of inheritable DNA lesions on genome transformation; G1408; WELLCOME TRUST; 104178/Z/14/Z
History
Publication status
- Published
File Version
- Published version
Journal
Nature CommunicationsISSN
2041-1723Publisher
Nature ResearchExternal DOI
Issue
1Volume
10Page range
1-17Department affiliated with
- Sussex Centre for Genome Damage Stability Publications
Research groups affiliated with
- Genome Damage and Stability Centre Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2019-06-25First Open Access (FOA) Date
2019-07-03First Compliant Deposit (FCD) Date
2019-06-24Usage metrics
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