The clockwork orange protein in fruit flies can both turn on and turn off clock gene activity

A null mutant of the clockwork orange (cwo) gene displays long-period activity rhythms.

• cwo loss of function leads to increased cwo mRNA levels.
• The mRNA peak levels of four known CLK/CYC target genes are reduced with cwo mutation.
• This mutation results in an almost complete loss of cycling for these target genes.
• Changes in the absence of CWO affect the phosphorylation cycles of PER and CLK.
• CWO appears to regulate clock gene expression by acting both as a repressor and an activator.

Simplified