Role of protein kinase PLK1 in the epigenetic maintenance of centromeres.
Duccio ContiArianna Esposito VerzaMarion E PesentiVerena CmentowskiIngrid R VetterDongqing PanAndrea MusacchioPublished in: Science (New York, N.Y.) (2024)
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 1 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 1 . Antithetically, Polo-like kinase 1 (PLK1) promotes CENP-A deposition in early G 1 , 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.
Keyphrases
- cell cycle
- cell proliferation
- protein kinase
- dna methylation
- gene expression
- single cell
- single molecule
- genome wide
- transcription factor
- stem cells
- liquid chromatography tandem mass spectrometry
- molecular dynamics simulations
- molecular dynamics
- cell therapy
- signaling pathway
- amino acid
- cell death
- mesenchymal stem cells
- mass spectrometry
- high resolution
- liquid chromatography
- small molecule
- pi k akt
- gas chromatography