Proper CycE–Cdk2 activity in endocycling tissues requires regulation of the cyclin-dependent kinase inhibitor Dacapo by dE2F1b in Drosophila

Abstract

Polyploidy is an integral part of development and is associated with cellular stress, aging, and pathological conditions. The endocycle, comprised of successive rounds of G and S phases without mitosis, is widely employed to produce polyploid cells in plants and animals. In Drosophila, maintenance of the endocycle is dependent on E2F-governed oscillations of Cyclin E (CycE)–Cdk2 activity, which is known to be largely regulated at the level of transcription. In this study, we report an additional level of E2F-dependent control of CycE–Cdk2 activity during the endocycle. Genetic experiments revealed that an alternative isoform of Drosophila de2f1, dE2F1b, regulates the expression of the p27CIP/KIP-like Cdk inhibitor Dacapo (Dap). We provide evidence showing that dE2F1b-dependent Dap expression in endocycling tissues is necessary for setting proper CycE–Cdk2 activity. Furthermore, we demonstrate that dE2F1b is required for proliferating cell nuclear antigen expression that establishes a negative feedback loop in S phase. Overall, our study reveals previously unappreciated E2F-dependent regulatory networks that are critical for the periodic transition between G and S phases during the endocycle.

Ca++ particle films on sweet potato plants: Repression of the cdc2a gene and alterations in leaf anatomy under photo-protection

“…The repression of the cdc2a gene in plants treated with the particle lm suggests protection against the harmful effects of UV radiation (Kim et al, 2021). The treatment may improve growth and productivity under stressful environmental conditions.…”

“…The expression of genes from the CDK family is critical for repairing and maintaining the integrity of the plant genome, as intense ultraviolet (UV) light can induce DNA damage by pyrimidine dimers (Kim et al, 2021). Therefore, the observed repression of the cdc2a gene in plants treated with the particle lm suggests that the treatment may provide additional protection against the harmful effects of UV radiation, leading to improved growth and productivity under stressful environmental conditions.…”

“…Within the set of stress-responsive genes, cdc2a, a homolog of cyclin-dependent protein kinase (CDK), plays a crucial role in regulating the cell cycle (Campo et al, 2014;Harashima and Sekine, 2020). In response to signaling cascades that perceive stress, cdc2a triggers cell division as a means of repairing, adapting, and enhancing the tolerance of plant tissues (Kim et al, 2021).…”

Super-resolution microscopy reveals stochastic initiation of replication in Drosophila polytene chromosomes

“…The reason may be that in contrast to diploid cells, the E2F (transcription regulator of many genes involved in the S-phase progression) acts upstream of cyclin E. In particular, the synthesis of ribonucleotide reductase is under control of E2F. It can be assumed that the ectopic expression of cyclin E triggers S phase without activating some genes necessary for the complete passage of the S phase (Edgar et al 2014 ; Kim et al 2021 ; Dimova and Dyson 2005 ). Possibly, that the cells enter the induced S phase with a limited amount of nucleotides.…”

E2F4 regulates the cell cycle and DNA replication in the silkworm, Bombyx mori

“…E2F family transcription factors not only play roles in mitosis, but are also important in the regulation of endoreduplication (De Veylder et al ., 2002; Zybina & Zybina, 2020). In Drosophila , the maintenance of the endocycle process depends on E2F‐mediated molecular oscillators of cyclin E/CDK2 activity (Zielke et al ., 2011; Kim et al ., 2021). E2F4 is a member of the canonical E2F transcription factor family and usually represents the predominant E2F activity in cells (Cuitiño et al ., 2019; Hsu et al ., 2019).…”