E2F/DP Prevents Cell-Cycle Progression in Endocycling Fat Body Cells by Suppressing dATM Expression

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Abstract

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 fat body, a differentiated tissue that grows via endocycles. We report an unexpected mechanism of E2F/DP action that promotes quiescence in this tissue. In the fat body, 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 fat body cells. Strikingly, reducing dATM levels in dDP-deficient fat bodies 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 for cell-cycle control and needed for normal development. Guarner et al. examine the consequences of eliminating E2F function in vivo in Drosophila and uncover a mechanism by which E2F maintains cell quiescence in the fat body, where highly differentiated cells grow via endocycles. E2F is required in the fat body to repress dATM and suppress DNA damage responses to limit cell-cycle progression.

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APA

Guarner, A., Morris, R., Korenjak, M., Boukhali, M., Zappia, M. P., Van Rechem, C., … Dyson, N. J. (2017). E2F/DP Prevents Cell-Cycle Progression in Endocycling Fat Body Cells by Suppressing dATM Expression. Developmental Cell, 43(6), 689-703.e5. https://doi.org/10.1016/j.devcel.2017.11.008

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