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Additional feedback loops in the Drosophila molecular clockwork. In addition to the principal PERIOD/TIMELESS (PER/TIM) feedback loop, CLOCK/CYCLE (CLK/CYC) also activate CLOCKWORK ORANGE (CWO), PAR DOMAIN PROTEIN 1 (PDP1), and VRILLE (VRI). CWO feeds back to repress CLK/CYC activation by binding to E-box elements (E). PDP1 activates the transcription of the Clk gene, whereas VRI competes with PDP1 binding to repress Clk expression. P/V domain denotes PDP/VRI-binding sites.
