Role of protein kinase PLK1 in the epigenetic maintenance of centromeres

Science. 2024 Sep 6;385(6713):1091-1097. doi: 10.1126/science.ado5178. Epub 2024 Sep 5.

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 G1 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 G1. Antithetically, Polo-like kinase 1 (PLK1) promotes CENP-A deposition in early G1, 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.

MeSH terms

  • Cell Cycle Proteins* / metabolism
  • Centromere Protein A* / metabolism
  • Centromere* / metabolism
  • Chromosomal Proteins, Non-Histone* / metabolism
  • Epigenesis, Genetic*
  • G1 Phase
  • HeLa Cells
  • Humans
  • Kinetochores / metabolism
  • Phosphorylation
  • Polo-Like Kinase 1* / genetics
  • Polo-Like Kinase 1* / metabolism
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism

Substances

  • Cell Cycle Proteins
  • CENPA protein, human
  • Centromere Protein A
  • Chromosomal Proteins, Non-Histone
  • Polo-Like Kinase 1
  • Proto-Oncogene Proteins
  • MIS18BP1 protein, human
  • MIS18A protein, human
  • PLK1 protein, human