TY - JOUR
T1 - Cyclin F suppresses B-Myb activity to promote cell cycle checkpoint control
AU - Klein, Ditte Kjærsgaard
AU - Hoffmann, Saskia
AU - Ahlskog, Johanna K
AU - O'Hanlon, Karen
AU - Quaas, Marianne
AU - Larsen, Brian D
AU - Rolland, Baptiste
AU - Rösner, Heike I
AU - Walter, David
AU - Kousholt, Arne Nedergaard
AU - Menzel, Tobias
AU - Lees, Michael
AU - Johansen, Jens Vilstrup
AU - Rappsilber, Juri
AU - Engeland, Kurt
AU - Sørensen, Claus Storgaard
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
U2 - 10.1038/ncomms6800
DO - 10.1038/ncomms6800
M3 - Journal article
C2 - 25557911
VL - 6
SP - 5800
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
ER -