2. Academic Validation
  3. Cyclin F suppresses B-Myb activity to promote cell cycle checkpoint control

Cyclin F suppresses B-Myb activity to promote cell cycle checkpoint control

  • Nat Commun. 2015 Jan 5;6:5800. doi: 10.1038/ncomms6800.
Ditte Kjærsgaard Klein 1,  Saskia Hoffmann 1,  Johanna K Ahlskog 1,  Karen O'Hanlon 1,  Marianne Quaas 2,  Brian D Larsen 1,  Baptiste Rolland 1,  Heike I Rösner 1,  David Walter 1,  Arne Nedergaard Kousholt 1,  Tobias Menzel 1,  Michael Lees 1,  Jens Vilstrup Johansen 1,  Juri Rappsilber 3,  Kurt Engeland 2,  Claus Storgaard Sørensen 1
Affiliations

Affiliations

  • 1 Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen N, Denmark.
  • 2 Department of Molecular Oncology, Medical School, University of Leipzig, Semmelweisstr. 14, 04103, Leipzig, Germany.
  • 3 Wellcome Trust Centre for Cell Biology, University of Edinburgh, Michael Swann Building, Kings Buildings, Mayfield Road, Edinburgh EH9 3JR, Scotland.
PMID: 25557911 DOI: 10.1038/ncomms6800
Abstract

Cells respond to DNA damage by activating cell cycle checkpoints to delay proliferation and facilitate DNA repair. Here, to uncover new checkpoint regulators, we perform RNA interference screening targeting genes involved in ubiquitylation processes. We show that the F-box protein cyclin F plays an important role in checkpoint control following ionizing radiation. Cyclin F-depleted cells initiate checkpoint signalling after ionizing radiation, but fail to maintain G2 phase arrest and progress into mitosis prematurely. Importantly, cyclin F suppresses the B-Myb-driven transcriptional programme that promotes accumulation of crucial mitosis-promoting proteins. Cyclin F interacts with B-Myb via the cyclin box domain. This interaction is important to suppress cyclin A-mediated phosphorylation of B-Myb, a key step in B-Myb activation. In summary, we uncover a regulatory mechanism linking the F-box protein cyclin F with suppression of the B-Myb/cyclin A pathway to ensure a DNA damage-induced checkpoint response in G2.

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