Figure 4.
Regulation of the Drosophila endocycle. A complex array of controls ensures once and only once replication during endocycle progression. The key players are shown when they are active (green, solid lines) or inactive (red, dashed lines) in either the G or S phase of the endocycle. Control of CycE/Cdk2 activity forms the core of endocycle regulation. CycE and CycE/Cdk2 activity are low during G phase when APC/Cfzr/cdh1 represses accumulation of Geminin, thereby allowing pre-RC formation. E2F stimulation of CycE transcription contributes to activation of CycE/Cdk2 and the initiation of DNA replication, which triggers E2F1 destruction. CycE/Cdk2 directly represses pre-RC formation and inactivates APC/Cfzr/cdh1, which allows Geminin accumulation that also inhibits pre-RC formation.