E2F/DP prevents cell cycle progression in endocycling fatbody cells by suppressing dATM expression

• Published in: Developmental cell Vol. 43; no. 6; pp. 689 - 703.e5
• Main Authors: Guarner, Ana, Morris, Robert, Korenjak, Michael, Boukhali, Myriam, Zappia, Maria Paula, Van Rechem, Capucine, Whetstine, Johnathan R., Ramaswamy, Sridhar, Zou, Lee, Frolov, Maxim V., Haas, Wilhelm, Dyson, Nicholas J.
• Format: Journal Article
• Language: English
• Published: 07.12.2017
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2017.11.008

To understand the consequences of the complete elimination of E2F regulation we profiled the proteome of Drosophila dDP mutants that lack functional E2F/DP complexes. The results uncovered changes in the larval fatbody, a differentiated tissue that grows via endocycles. We report an unexpected mechanism of E2F/DP action that promotes quiescence in this tissue. In the fatbody, dE2F/dDP limits cell cycle progression by suppressing DNA damage responses. Loss of dDP upregulates dATM, allowing cells to sense and repair DNA damage, and increasing replication of loci that are normally under-replicated in wild-type tissues. Genetic experiments show that ectopic dATM is sufficient to promote DNA synthesis in wild-type fatbody cells. Strikingly, reducing dATM levels in dDP-deficient fatbodies restores cell cycle control, improves tissue morphology and extends animal development. These results show that, in some cellular contexts, dE2F/dDP-dependent suppression of DNA damage signaling is key to cell cycle control and needed for normal development.