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).