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

Ditte Kjærsgaard Klein; Saskia Hoffmann; Johanna K Ahlskog; Karen O'Hanlon; Marianne Quaas; Brian D Larsen; Baptiste Rolland; Heike I Rösner; David Walter; Arne Nedergaard Kousholt; Tobias Menzel; Michael Lees; Jens Vilstrup Johansen; Juri Rappsilber; Kurt Engeland; Claus Storgaard Sørensen

doi:10.1038/ncomms6800

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

Ditte Kjærsgaard Klein, Saskia Hoffmann, Johanna K Ahlskog, Karen O'Hanlon, Marianne Quaas, Brian D Larsen, Baptiste Rolland, Heike I Rösner, David Walter, Arne Nedergaard Kousholt, Tobias Menzel, Michael Lees, Jens Vilstrup Johansen, Juri Rappsilber, Kurt Engeland, Claus Storgaard Sørensen

38 Citations (Scopus)

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.

Original language	English
Journal	Nature Communications
Volume	6
Pages (from-to)	5800
ISSN	2041-1723
DOIs	https://doi.org/10.1038/ncomms6800
Publication status	Published - 5 Jan 2015

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Klein, D. K., Hoffmann, S., Ahlskog, J. K., O'Hanlon, K., Quaas, M., Larsen, B. D., Rolland, B., Rösner, H. I., Walter, D., Kousholt, A. N., Menzel, T., Lees, M., Johansen, J. V., Rappsilber, J., Engeland, K., & Sørensen, C. S. (2015). Cyclin F suppresses B-Myb activity to promote cell cycle checkpoint control. Nature Communications, 6, 5800. https://doi.org/10.1038/ncomms6800

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title = "Cyclin F suppresses B-Myb activity to promote cell cycle checkpoint control",

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.",

author = "Klein, {Ditte Kj{\ae}rsgaard} and Saskia Hoffmann and Ahlskog, {Johanna K} and Karen O'Hanlon and Marianne Quaas and Larsen, {Brian D} and Baptiste Rolland and R{\"o}sner, {Heike I} and David Walter and Kousholt, {Arne Nedergaard} and Tobias Menzel and Michael Lees and Johansen, {Jens Vilstrup} and Juri Rappsilber and Kurt Engeland and S{\o}rensen, {Claus Storgaard}",

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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 - 2015/1/5

Y1 - 2015/1/5

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

SN - 2041-1723

VL - 6

SP - 5800

JO - Nature Communications

JF - Nature Communications

ER -

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

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