A detailed map of coupled circadian clock and cell cycle with qualitative dynamics validation - Inserm - Institut national de la santé et de la recherche médicale Accéder directement au contenu
Article Dans Une Revue BMC Bioinformatics Année : 2021

A detailed map of coupled circadian clock and cell cycle with qualitative dynamics validation

Résumé

Background: The temporal coordination of biological processes by the circadian clock is an important mechanism, and its disruption has negative health outcomes, including cancer. Experimental and theoretical evidence suggests that the oscillators driving the circadian clock and the cell cycle are coupled through phase locking. Results: We present a detailed and documented map of known mechanisms related to the regulation of the circadian clock, and its coupling with an existing cell cycle map which includes main interactions of the mammalian cell cycle. The coherence of the merged map has been validated with a qualitative dynamics analysis. We verified that the coupled circadian clock and cell cycle maps reproduce the observed sequence of phase markers. Moreover, we predicted mutations that contribute to regulating checkpoints of the two oscillators. Conclusions: Our approach underlined the potential key role of the core clock protein NR1D1 in regulating cell cycle progression. We predicted that its activity influences negatively the progression of the cell cycle from phase G2 to M. This is consistent with the earlier experimental finding that pharmacological activation of NR1D1 inhibits tumour cell proliferation and shows that our approach can identify biologically relevant species in the context of large and complex networks.
Fichier principal
Vignette du fichier
Rougny2021_Article_ADetailedMapOfCoupledCircadian.pdf (1.56 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

inserm-03228503 , version 1 (18-05-2021)

Identifiants

Citer

Adrien Rougny, Loïc Paulevé, Michèle Teboul, Franck Delaunay. A detailed map of coupled circadian clock and cell cycle with qualitative dynamics validation. BMC Bioinformatics, 2021, 22 (1), pp.240. ⟨10.1186/s12859-021-04158-9⟩. ⟨inserm-03228503⟩
65 Consultations
105 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More