Wake-sleep cycles are severely disrupted by diseases affecting cytoplasmic homeostasis.

ABSTRACT: The circadian clock is based on a transcriptional feedback loop with an essential time delay before feedback inhibition. Previous work has shown that PERIOD (PER) proteins generate circadian time cues through rhythmic nuclear accumulation of the inhibitor complex and subsequent interaction with the activator complex in the feedback loop. Although this temporal manifestation of the feedback inhibition is the direct consequence of PER's cytoplasmic trafficking before nuclear entry, how this spatial regulation of the pacemaker affects circadian timing has been largely unexplored. Here we show that circadian rhythms, including wake-sleep cycles, are lengthened and severely unstable if the cytoplasmic trafficking of PER is disrupted by any disease condition that leads to increased congestion in

SUBMITTER: Beesley S 

PROVIDER: S-EPMC7668169 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature