For CRYing out loud!

The genetic network of the transcriptional/translational feedback loop that creates circadian rhythms in animals was outlined well over a decade ago. However, we still don't understand transitions through distinct transcriptional regulatory complexes are orchestrated throughout the day because we don't yet know how these dedicated clock proteins interact with one another. In collaboration with Greg Hura, Dina Schneidman-Duhovny and Joe Takahashi, we set out to identify how the circadian repressor CRY1 is recruited to CLOCK:BMAL1 to hold off transcriptional activation until the right time of day. Using a combination of x-ray crystallography, small angle x-ray scattering and good old fashioned biochemistry, we showed that CRY1 docks onto the CLOCK:BMAL1 complex with its secondary pocket, an evolutionary remnant from its ancestor DNA photolyase. Alicia and Jenny's paper came online today at PNAS -- check it out @ doi:10.1073/pnas.1615310114.