scholarly journals Circadian Clock Synchronization of the Cell Cycle in Zebrafish Occurs through a Gating Mechanism Rather Than a Period-phase Locking Process

2018 ◽  
Vol 33 (2) ◽  
pp. 137-150 ◽  
Author(s):  
Ricardo Laranjeiro ◽  
T. Katherine Tamai ◽  
William Letton ◽  
Noémie Hamilton ◽  
David Whitmore
Keyword(s):  
Cell Cycle ◽  
Circadian Clock ◽  
Clock Synchronization ◽  
Phase Locking ◽  
Gating Mechanism

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

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Adrien Rougny ◽  
Loïc Paulevé ◽  
Michèle Teboul ◽  
Franck Delaunay
Keyword(s):  
Cell Cycle ◽  
Circadian Clock ◽  
Cell Cycle Progression ◽  
Phase Locking ◽  
Biologically Relevant ◽  
Mammalian Cell Cycle ◽  
Qualitative Dynamics ◽  
Theoretical Evidence ◽  
Negative Health Outcomes

Abstract 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.

scholarly journals A Detailed Map of Coupled Circadian Clock and Cell Cycle with Qualitative Dynamics Validation

2020 ◽  
Author(s):  
Adrien Rougny ◽  
Loïc Paulevé ◽  
Michèle Teboul ◽  
Franck Delaunay
Keyword(s):  
Cell Cycle ◽  
Circadian Clock ◽  
Cell Cycle Progression ◽  
Phase Locking ◽  
Biologically Relevant ◽  
Mammalian Cell Cycle ◽  
Qualitative Dynamics ◽  
Theoretical Evidence ◽  
Negative Health Outcomes

AbstractThe 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. We present a detailed and documented SBGN PD map of known mechanisms related to the regulation of the circadian clock, and its coupling with an existing cell cycle SBGN PD 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 allow reproducing the observed sequence of phase markers. Moreover, we predicted mutations that contribute to regulating checkpoints of the two oscillators. Strikingly, our approach underlines 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. It 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.

scholarly journals Role of the circadian clock "Death-Loop" in the DNA damage response underpinning cancer treatment resistance

2022 ◽  
Author(s):  
Ninel Miriam Vainshelbaum ◽  
Kristine Salmina ◽  
Bogdan I Gerashchenko ◽  
Marija Lazovska ◽  
Pawel Zayakin ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Circadian Clock ◽  
Cancer Cells ◽  
Dna Damage Response ◽  
Embryonic Stem ◽  
Early Embryo ◽  
Mitotic Slippage ◽  
Damage Response ◽  
Telomere Regulation

The Circadian Clock (CC) drives the normal cell cycle and reciprocally regulates telomere elongation. However, it can be deregulated in cancer, embryonic stem cells (ESC) and the early embryo. Here, its role in the resistance of cancer cells to genotoxic treatments was assessed in relation to whole-genome duplication (WGD) and telomere regulation. We first evaluated the DNA damage response of polyploid cancer cells and observed a similar impact on the cell cycle to that seen in ESC - overcoming G1/S, adapting DNA damage checkpoints, tolerating DNA damage, and coupling telomere erosion to accelerated cell senescence, favouring transition by mitotic slippage into the ploidy cycle (reversible polyploidy). Next, we revealed a positive correlation between cancer WGD and deregulation of CC assessed by bioinformatics on 11 primary cancer datasets (rho=0.83; p<0.01). As previously shown, the cancer cells undergoing mitotic slippage cast off telomere fragments with TERT, restore the telomeres by recombination and return their depolyploidised mitotic offspring to TERT-dependent telomere regulation. Through depolyploidisation and the CC "death loop", the telomeres and Hayflick limit count are thus again renewed. This mechanism along with similar inactivity of the CC in early embryos supports a life-cycle (embryonic) concept of cancer.

scholarly journals Circadian regulation of c-MYC in mice

2020 ◽  
Vol 117 (35) ◽  
pp. 21609-21617
Author(s):  
Zhenxing Liu ◽  
Christopher P. Selby ◽  
Yanyan Yang ◽  
Laura A. Lindsey-Boltz ◽  
Xuemei Cao ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Circadian Clock ◽  
Tumor Suppressors ◽  
Feedback Loop ◽  
Cell Cycle Progression ◽  
Regulatory Mechanism ◽  
Clock Genes ◽  
Circadian Regulation ◽  
Cycle Progression ◽  
Insight Into

The circadian clock is a global regulatory mechanism that controls the expression of 50 to 80% of transcripts in mammals. Some of the genes controlled by the circadian clock are oncogenes or tumor suppressors. Among theseMychas been the focus of several studies which have investigated the effect of clock genes and proteins onMyctranscription and MYC protein stability. Other studies have focused on effects ofMycmutation or overproduction on the circadian clock in comparison to their effects on cell cycle progression and tumorigenesis. Here we have used mice with mutations in the essential clock genesBmal1,Cry1,andCry2to gain further insight into the effect of the circadian clock on this important oncogene/oncoprotein and tumorigenesis. We find that mutation of bothCry1andCry2, which abolishes the negative arm of the clock transcription–translation feedback loop (TTFL), causes down-regulation of c-MYC, and mutation ofBmal1,which abolishes the positive arm of TTFL, causes up-regulation of the c-MYC protein level in mouse spleen. These findings must be taken into account in models of the clock disruption–cancer connection.

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