Usually, each step in the cell cycle depends on the completion of the previous stage. But some cells – for example, cardiomyocytes, Drosophila egg follicle cells and many cancer cells – can endocycle, where DNA synthesis continues without mitosis. On p. 3169, Shcherbata and colleagues investigate how Notch signalling controls the mitotic-to-endocytic transition in Drosophila follicle cells at mid-oogenesis. By identifying genes whose transcription is responsive to Notch at this transition, the researchers show that Notch activity: (1) blocks the mitotic (M) phase of the cycle by downregulating the G2/M regulator String;(2) allows G1 entry by activating Hec/CdhFrz, a regulator of the APC ubiquitination complex; and (3) ensures S-phase entry by repressing Dacapo, a cyclinE/CDK complex inhibitor. As the researchers discuss, a better understanding of how external signalling pathways control physiological cell-cycle transitions could identify how abnormal cell-cycle control occurs in cancer cells.

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