APC/CFzr/Cdh1 promotes cell cycle progression during the Drosophila endocycle

Karine Narbonne-Reveau, Stefania Senger, Margit Pal, Anabel Herr, Helena E. Richardson, Maki Asano, Peter Deak, Mary A. Lilly

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Abstract

The endocycle is a commonly observed variant cell cycle in which cells undergo repeated rounds of DNA replication with no intervening mitosis. How the cell cycle machinery is modified to transform a mitotic cycle into endocycle has long been a matter of interest. In both plants and animals, the transition from the mitotic cycle to the endocycle requires Fzr/Cdh1, a positive regulator of the Anaphase-Promoting Complex/ Cyclosome (APC/C). However, because many of its targets are transcriptionally downregulated upon entry into the endocycle, it remains unclear whether the APC/C functions beyond the mitotic/endocycle boundary. Here, we report that APC/CFzr/Cdh1 activity is required to promote the G/S oscillation of the Drosophila endocycle. We demonstrate that compromising APC/C activity, after cells have entered the endocycle, inhibits DNA replication and results in the accumulation of multiple APC/C targets, including the mitotic cyclins and Geminin. Notably, our data suggest that the activity of APC/CFzr/Cdh1 during the endocycle is not continuous but is cyclic, as demonstrated by the APC/C-dependent oscillation of the pre-replication complex component Orc1. Taken together, our data suggest a model in which the cyclic activity of APC/CFzr/Cdh1 during the Drosophila endocycle is driven by the periodic inhibition of Fzr/Cdh1 by Cyclin E/Cdk2. We propose that, as is observed in mitotic cycles, during endocycles, ApC/ CFzr/Cdh1 functions to reduce the levels of the mitotic cyclins and Geminin in order to facilitate the relicensing of DNA replication origins and cell cycle progression.

Original languageEnglish
Pages (from-to)1451-1461
Number of pages11
JournalDevelopment
Volume135
Issue number8
DOIs
Publication statusPublished - Apr 1 2008

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Keywords

  • APC/C
  • Cdh1
  • Cyclin E
  • Drosophila
  • Endocycle
  • Endoreplication
  • Fzr/Cdh1
  • Geminin

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

Cite this

Narbonne-Reveau, K., Senger, S., Pal, M., Herr, A., Richardson, H. E., Asano, M., Deak, P., & Lilly, M. A. (2008). APC/CFzr/Cdh1 promotes cell cycle progression during the Drosophila endocycle. Development, 135(8), 1451-1461. https://doi.org/10.1242/dev.016295