Figures
DNA damage induces phase advances in the circadian clock.
DNA damage in mammalian cells leads to activation of the cell cycle regulator Chk2, which triggers downstream degradations of a core clock component, PER (i.e., PER1 in mice). This, in turn, creates unique phase shifts (mostly advances) in the circadian clock. Computational analyses from Hong et al. (doi:10.1371/journal.pcbi.1000384) recapitulate a phase advance (dashed curve) when DNA damage occurs around the peak of PER abundance, but minimum phase shifts around the trough (dots). The model proposes a molecular mechanism behind this phenomenon: differential degradation of PER in the presence of an essential positive feedback loop in the circadian system.
Image Credit: Judit Zámborszky (CoSBi, Microsoft Research-University of Trento Centre for Computational and Systems Biology, Italy).
Citation: (2009) PLoS Computational Biology Issue Image | Vol. 5(5) May 2009. PLoS Comput Biol 5(5): ev05.i05. https://doi.org/10.1371/image.pcbi.v05.i05
Published: May 29, 2009
Copyright: © 2009 Hong et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DNA damage in mammalian cells leads to activation of the cell cycle regulator Chk2, which triggers downstream degradations of a core clock component, PER (i.e., PER1 in mice). This, in turn, creates unique phase shifts (mostly advances) in the circadian clock. Computational analyses from Hong et al. (doi:10.1371/journal.pcbi.1000384) recapitulate a phase advance (dashed curve) when DNA damage occurs around the peak of PER abundance, but minimum phase shifts around the trough (dots). The model proposes a molecular mechanism behind this phenomenon: differential degradation of PER in the presence of an essential positive feedback loop in the circadian system.
Image Credit: Judit Zámborszky (CoSBi, Microsoft Research-University of Trento Centre for Computational and Systems Biology, Italy).