Fig. 2.

The endoreplication oscillator in Drosophila salivary glands. The core regulatory relationships between E2f1, Cyclin E and CRL4^Cdt2 (top) give rise to out-of-phase oscillations in the activity of key regulatory proteins controlling S phase (bottom). E2f1, APC^Fzr/Cdh1 and Cdt1 (red) are active during G phase, whereas the Cyclin E/Cdk2 complex, CRL4^Cdt2 and Geminin (black) are active during S phase. Note that CRL4^Cdt2 activity is dependent on DNA replication, which is triggered by the Cyclin E/Cdk2 complex, and that Cdt1 is inhibited both by Geminin binding and CRL4^Cdt2-mediated destruction.