The discovery of cryptochromes (CRY) and the identification of the PERIOD (PER) and TIMELESS (TIM) genes filled considerable gaps in our understanding of how the circadian clock functions in plants and animals. However, our understanding of the core circadian clock circuit was lacking a component that responds to light and regulates the activity of the PER-TIM complex. This missing piece of the clock puzzle was finally discovered with the identification of CHRONO, a protein that plays a key role in light input to the core clock.

Chrono and the Light Input Pathway

Chrono, also known as CRYPTOCHROME INTERACTING 1 (CRY1) in plants and CRYPTOCHROME 2 (CRY2) in mammals, is a flavin-binding photoreceptor that is involved in the light-dependent regulation of the circadian clock. In both plants and animals, Chrono physically interacts with the CRYPTOCHROME (CRY) photoreceptor and acts as a signal transducer that relays information about light exposure to the core clock components.

Upon exposure to light, CRY undergoes a conformational change that alters its interaction with Chrono. This change modulates the activity of the PER-TIM complex, leading to the regulation of clock-controlled gene expression and the synchronization of the clock with the light-dark cycle. Specifically, Chrono plays crucial roles in:

Light-induced degradation of TIM: Cryptochromes in their active state facilitate the ubiquitination and subsequent degradation of TIM. This degradation is particularly important during the day, resetting the clock and preparing it for the next cycle.

Phosphorylation of PER: Chrono also promotes the light-dependent phosphorylation of PER, which influences the stability and activity of the PER-TIM complex and regulates the timing of clock gene expression.

Circadian regulation of CRY expression: Chrono is itself under the control of the circadian clock, forming a feedback loop that enhances the robustness and precision of the circadian timekeeping mechanism.

Chrono in Plant and Mammalian Circadian Systems

In plants, Chrono is a key component of the light input pathway that ensures the proper synchronization of the circadian clock with the changing day and night conditions. It plays a particularly crucial role in the regulation of shade avoidance responses, helping plants to optimize their growth and development based on light availability.

In mammals, Chrono is expressed in the suprachiasmatic nucleus (SCN), the central circadian clock of the brain, where it contributes to the regulation of sleep-wake cycles and other physiological processes with circadian rhythms. Mutations or disruptions in Chrono have been linked to sleep disturbances, highlighting the significance of this protein in the mammalian circadian system.

In conclusion, the identification and characterization of Chrono filled a crucial gap in our understanding of the circadian clock circuit, providing insights into the molecular mechanisms underlying light input to the clock. Chrono serves as a key link between light perception and the regulation of core clock components, ensuring that organisms can align their biological rhythms with the external environment to optimize their survival and fitness.