Metabolic Regulation of Developmental Cell Cycles and Zygotic Transcription

Nareg J.V. Djabrayan, Celia M. Smits, Matej Krajnc, Tomer Stern, Shigehiro Yamada, William C. Lemon, Philipp J. Keller, Christine A. Rushlow, Stanislav Y. Shvartsman

Research output: Contribution to journalArticle

Abstract

The thirteen nuclear cleavages that give rise to the Drosophila blastoderm are some of the fastest known cell cycles [1]. Surprisingly, the fertilized egg is provided with at most one-third of the dNTPs needed to complete the thirteen rounds of DNA replication [2]. The rest must be synthesized by the embryo, concurrent with cleavage divisions. What is the reason for the limited supply of DNA building blocks? We propose that frugal control of dNTP synthesis contributes to the well-characterized deceleration of the cleavage cycles and is needed for robust accumulation of zygotic gene products. In support of this model, we demonstrate that when the levels of dNTPs are abnormally high, nuclear cleavages fail to sufficiently decelerate, the levels of zygotic transcription are dramatically reduced, and the embryo catastrophically fails early in gastrulation. Our work reveals a direct connection between metabolism, the cell cycle, and zygotic transcription.

Original languageEnglish (US)
Pages (from-to)1193-1198.e5
JournalCurrent Biology
Volume29
Issue number7
DOIs
StatePublished - Apr 1 2019

Keywords

  • DNA replication
  • Drosophila
  • MZT
  • RNR
  • cell-cycle control
  • metabolism
  • morphogenesis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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  • Cite this

    Djabrayan, N. J. V., Smits, C. M., Krajnc, M., Stern, T., Yamada, S., Lemon, W. C., Keller, P. J., Rushlow, C. A., & Shvartsman, S. Y. (2019). Metabolic Regulation of Developmental Cell Cycles and Zygotic Transcription. Current Biology, 29(7), 1193-1198.e5. https://doi.org/10.1016/j.cub.2019.02.028