Role of protein kinase PLK1 in the epigenetic maintenance of centromeres

The centromere, a chromosome locus defined by the histone H3-like protein centromeric protein A (CENP-A), promotes assembly of the kinetochore to bind microtubules during cell division. Centromere maintenance requires CENP-A to be actively replenished by dedicated protein machinery in the early G<sub>1</sub> phase of the cell cycle to compensate for its dilution after DNA replication. Cyclin-dependent kinases (CDKs) limit CENP-A deposition to once per cell cycle and function as negative regulators outside of early G<sub>1</sub>. Antithetically, Polo-like kinase 1 (PLK1) promotes CENP-A deposition in early G<sub>1</sub>, but the molecular details of this process are still unknown. We reveal here 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 clarify how PLK1 contributes to the epigenetic maintenance of centromeres.

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Publication Details

Journal
Science
Published
2024-09-05
DOI
https://doi.org/10.1126/science.ado5178
Citations
29
Primary Topic
Microtubule and mitosis dynamics
Type
article
Field-Weighted Citation Impact
9.45
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article

Role of protein kinase PLK1 in the epigenetic maintenance of centromeres

Duccio Conti, Ingrid R. Vetter, Dongqing Pan, Verena Cmentowski et al.
29 citations
Science
Microtubule and mitosis dynamics
9.45
article

Role of protein kinase PLK1 in the epigenetic maintenance of centromeres

Duccio Conti, Ingrid R. Vetter, Dongqing Pan, Verena Cmentowski, Marion E. Pesenti
article en
29 citations

Abstract

The centromere, a chromosome locus defined by the histone H3-like protein centromeric protein A (CENP-A), promotes assembly of the kinetochore to bind microtubules during cell division. Centromere maintenance requires CENP-A to be actively replenished by dedicated protein machinery in the early G<sub>1</sub> phase of the cell cycle to compensate for its dilution after DNA replication. Cyclin-dependent kinases (CDKs) limit CENP-A deposition to once per cell cycle and function as negative regulators outside of early G<sub>1</sub>. Antithetically, Polo-like kinase 1 (PLK1) promotes CENP-A deposition in early G<sub>1</sub>, but the molecular details of this process are still unknown. We reveal here 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 clarify how PLK1 contributes to the epigenetic maintenance of centromeres.

ScienceVol. 385(6713)
Max Planck Institute of Molecular Physiology (DE), University of Duisburg-Essen (DE)
Openalex Percentile: Top 1%
Microtubule and mitosis dynamics
9.45
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