DNA-protein interactions: genome-wide binding profile (ChIP-chip) assayed for cyc protein in adult heads; see GEO_GSE32613 (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE32613).

Clk and cyc proteins interact in the cytoplasm of S2R+ cells and heterodimerisation promotes nuclear import as well as phosphorylation of cytoplasmic Clk protein.

cry functions as a repressor of Clk/cyc-activated transcription.

dco-mediated hyperphosphorylation of Clk does not require cyc or the DNA-binding domain of Clk.

Clk and cyc, along with other circadian genes per and dco (but not tim) have roles in regulating cocaine sensitization and may function as regulators of Tdc.

Sensitization to repeated cocaine exposures, a phenomenon also seen in humans and animal models and associated with enhanced drug craving, is eliminated in flies mutant for per, dco, Clk, and cyc but not tim.

Clk mRNA cycling is regulated by per-tim-mediated release of Clk- and cyc-dependent repression.

Daily cycles in the association of per and tim proteins with the Clk-cyc complex may contribute to rhythmic expression of per and tim.

The tim-induced per mRNA level increase does not require cyc.

Mutation of the cyc gene produces flies that are behaviourally arrhythmic and have little per or tim transcription.

Arrhythmic mutant. per and tim transcription levels are low and constant in cyc mutants.