How does light synchronise the molecular clock works?

Most clock genes are expressed in a rhythmic fashion, meaning that like the biological processes they control, their expression reaches peak and trough values once during a 24-hr day (Stanewsky et al., 2003). In order to adjust these molecular oscillations to changing environmental conditions (for example the seasonal changes of day length), clock gene expression must somehow respond to changes in illumination.

In flies, the clock protein Timeless (Tim) is degraded upon light-exposure. Since Tim is required to stabilize the clock protein Period (Per), the whole molecular oscillations are reset according to the light-dependent degradation of Tim.
Therefore, light-signalling to Tim is a crucial step in light-resetting. Cry is probably the major photoreceptor mediating this task. Upon illumination Cry is thought to undergo a conformational change allowing it to bind to Tim. As a consequence both Tim and Cry become a substrate for the F-box protein Jetlag (Jet) and are subsequently degraded by the proteasome (Peschel et al., 2006, 2009). Although the light-dependent Cry/Tim/Jet interactions (Figure) are arguably a crucial part of the molecular light-resetting apparatus, it is clear that Tim degradation can also be achieved by a Cry-independent pathway, because some clock neurons are ‘immune’ to a lack of Cry function (Stanewsky et al., 1998; Helfrich-Foerster et al., 2001; Veleri et al., 2007). Current projects in our lab aim to identify both, novel factors mediating this alternative resetting pathway, and additional ones contributing to the Cry/Tim/Jet pathway.