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 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

Fingerprint

Transcription
cell cycle
Cell Cycle
embryo (animal)
Embryonic Structures
transcription (genetics)
Cells
Blastoderm
blastoderm
Gastrulation
Deceleration
Zygote
DNA
DNA replication
DNA Replication
Metabolism
Drosophila
Genes
metabolism
synthesis

Keywords

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

ASJC Scopus subject areas

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

Cite this

Djabrayan, N. J. V., Smits, C. M., Krajnc, M., Stern, T., Yamada, S., Lemon, W. C., ... 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

Metabolic Regulation of Developmental Cell Cycles and Zygotic Transcription. / Djabrayan, Nareg J.V.; Smits, Celia M.; Krajnc, Matej; Stern, Tomer; Yamada, Shigehiro; Lemon, William C.; Keller, Philipp J.; Rushlow, Christine; Shvartsman, Stanislav Y.

In: Current Biology, Vol. 29, No. 7, 01.04.2019, p. 1193-1198.e5.

Research output: Contribution to journalArticle

Djabrayan, NJV, Smits, CM, Krajnc, M, Stern, T, Yamada, S, Lemon, WC, Keller, PJ, Rushlow, C & Shvartsman, SY 2019, 'Metabolic Regulation of Developmental Cell Cycles and Zygotic Transcription', Current Biology, vol. 29, no. 7, pp. 1193-1198.e5. https://doi.org/10.1016/j.cub.2019.02.028
Djabrayan NJV, Smits CM, Krajnc M, Stern T, Yamada S, Lemon WC et al. Metabolic Regulation of Developmental Cell Cycles and Zygotic Transcription. Current Biology. 2019 Apr 1;29(7):1193-1198.e5. https://doi.org/10.1016/j.cub.2019.02.028
Djabrayan, Nareg J.V. ; Smits, Celia M. ; Krajnc, Matej ; Stern, Tomer ; Yamada, Shigehiro ; Lemon, William C. ; Keller, Philipp J. ; Rushlow, Christine ; Shvartsman, Stanislav Y. / Metabolic Regulation of Developmental Cell Cycles and Zygotic Transcription. In: Current Biology. 2019 ; Vol. 29, No. 7. pp. 1193-1198.e5.
@article{20d7252fd692418ebbbbd78280aaf3d3,
title = "Metabolic Regulation of Developmental Cell Cycles and Zygotic Transcription",
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.",
keywords = "cell-cycle control, DNA replication, Drosophila, metabolism, morphogenesis, MZT, RNR",
author = "Djabrayan, {Nareg J.V.} and Smits, {Celia M.} and Matej Krajnc and Tomer Stern and Shigehiro Yamada and Lemon, {William C.} and Keller, {Philipp J.} and Christine Rushlow and Shvartsman, {Stanislav Y.}",
year = "2019",
month = "4",
day = "1",
doi = "10.1016/j.cub.2019.02.028",
language = "English (US)",
volume = "29",
pages = "1193--1198.e5",
journal = "Current Biology",
issn = "0960-9822",
publisher = "Cell Press",
number = "7",

}

TY - JOUR

T1 - Metabolic Regulation of Developmental Cell Cycles and Zygotic Transcription

AU - Djabrayan, Nareg J.V.

AU - Smits, Celia M.

AU - Krajnc, Matej

AU - Stern, Tomer

AU - Yamada, Shigehiro

AU - Lemon, William C.

AU - Keller, Philipp J.

AU - Rushlow, Christine

AU - Shvartsman, Stanislav Y.

PY - 2019/4/1

Y1 - 2019/4/1

N2 - 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.

AB - 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.

KW - cell-cycle control

KW - DNA replication

KW - Drosophila

KW - metabolism

KW - morphogenesis

KW - MZT

KW - RNR

UR - http://www.scopus.com/inward/record.url?scp=85063344191&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85063344191&partnerID=8YFLogxK

U2 - 10.1016/j.cub.2019.02.028

DO - 10.1016/j.cub.2019.02.028

M3 - Article

C2 - 30880009

AN - SCOPUS:85063344191

VL - 29

SP - 1193-1198.e5

JO - Current Biology

JF - Current Biology

SN - 0960-9822

IS - 7

ER -