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bioRxiv · 10.1101/2024.02.23.581696

Role of PLK1 in the epigenetic maintenance of centromeres

Conti, D.·Esposito Verza, A.·Pesenti, M. E.·Cmentowski, V.·Vetter, I. R.·Pan, D.·Musacchio, A.
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Abstract

The centromere, a chromosome locus defined by the histone H3-like protein CENP-A, seeds the kinetochore to bind microtubules during cell division. Centromere maintenance requires CENP-A to be actively replenished by dedicated protein machinery in the early G1 cell-cycle phase, compensating for its two-fold dilution following DNA replication. Cyclin-dependent kinases (CDKs) limit CENP-A deposition to once per cell cycle and function as negative regulators outside early G1. Antithetically, Polo-like kinase 1 (PLK1) promotes CENP-A deposition in early G1, but the molecular details are still unknown. We reveal a phosphorylation network that recruits PLK1 to the deposition machinery to control a conformational switch required for licensing the CENP-A deposition reaction. Our findings solve the long-standing question of how PLK1 contributes to the epigenetic maintenance of centromeres. One-Sentence SummaryPLK1 licenses epigenetic maintenance of centromeres by regulating a conformational switch on the MIS18 protein.

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Conti, D., Esposito Verza, A., Pesenti, M. E., Cmentowski, V., Vetter, I. R., Pan, D., Musacchio, A.. 2024-02-23. Role of PLK1 in the epigenetic maintenance of centromeres. https://doi.org/10.1101/2024.02.23.581696

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