Cell-cycle phospho-regulation of the kinetochore

Abstract

The kinetochore is a mega-dalton protein assembly that forms within centromeric regions of chromosomes and directs their segregation during cell division. Here we review cell cycle-mediated phosphorylation events at the kinetochore, with a focus on the budding yeast Saccharomyces cerevisiae and the insight gained from forced associations of kinases and phosphatases. The point centromeres found in the budding yeast S. cerevisiae are one of the simplest such structures found in eukaryotes. The S. cerevisiae kinetochore comprises a single nucleosome, containing a centromere-specific H3 variant Cse4CENP-A, bound to a set of kinetochore proteins that connect to a single microtubule. Despite the simplicity of the budding yeast kinetochore, the proteins are mostly homologous with their mammalian counterparts. In some cases, human proteins can complement their yeast orthologs. Like its mammalian equivalent, the regulation of the budding yeast kinetochore is complex: integrating signals from the cell cycle, checkpoints, error correction, and stress pathways. The regulatory signals from these diverse pathways are integrated at the kinetochore by post-translational modifications, notably phosphorylation and dephosphorylation, to control chromosome segregation. Here we highlight the complex interplay between the activity of the different cell-cycle kinases and phosphatases at the kinetochore, emphasizing how much more we have to understand this essential structure.

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Acknowledgements

The authors acknowledge funding from the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001003), the UK Medical Research Council (FC001003) and the Wellcome Trust (FC001003). C.K. is supported via a studentship from the School of Biological and Chemical Sciences at Queen Mary University of London. We would like to thank Frank Uhlmann and John Diffley for comments on this review. We are indebted to an anonymous reviewer whose comments greatly improved this review.

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Klemm, C., Thorpe, P.H. & Ólafsson, G. Cell-cycle phospho-regulation of the kinetochore. Curr Genet (2020). https://doi.org/10.1007/s00294-020-01127-2

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Keywords

  • Kinetochore regulation
  • Phosphorylation
  • Polo-like kinase
  • Cdc5
  • DDK
  • Cdc14
  • CDK
  • CK2
  • PP1
  • PP2A