Dynamic Control of dNTP Synthesis in Early Embryos

Yonghyun Song, Robert A. Marmion, Junyoung O. Park, Debopriyo Biswas, Joshua D. Rabinowitz, Stanislav Yefimovic Shvartsman

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Exponential increase of cell numbers in early embryos requires large amounts of DNA precursors (deoxyribonucleoside triphosphates (dNTPs)). Little is understood about how embryos satisfy this demand. We examined dNTP metabolism in the early Drosophila embryo, in which gastrulation is preceded by 13 sequential nuclear cleavages within only 2 hr of fertilization. Surprisingly, despite the breakneck speed at which Drosophila embryos synthesize DNA, maternally deposited dNTPs can generate less than half of the genomes needed to reach gastrulation. The rest of the dNTPs are synthesized “on the go.” The rate-limiting enzyme of dNTP synthesis, ribonucleotide reductase, is inhibited by endogenous levels of deoxyATP (dATP) present at fertilization and is activated as dATP is depleted via DNA polymerization. This feedback inhibition renders the concentration of dNTPs at gastrulation robust, with respect to large variations in maternal supplies, and is essential for normal progression of embryogenesis.

Original languageEnglish (US)
Pages (from-to)301-308.e3
JournalDevelopmental cell
Volume42
Issue number3
DOIs
StatePublished - Aug 7 2017

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

Keywords

  • Drosophila
  • dNTP metabolism
  • embryogenesis
  • feedback inhibition
  • ribonucleotide reductase

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