TitleDynamic Control of dNTP Synthesis in Early Embryos.
Publication TypeJournal Article
Year of Publication2017
AuthorsSong, Y, Marmion, RA, Park, JO, Biswas, D, Rabinowitz, JD, Shvartsman, SY
JournalDev Cell
Date Published2017 Aug 07
KeywordsAnimals, Deoxyribonucleotides, Drosophila, Embryonic Development, Feedback, Physiological

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.

Alternate JournalDev. Cell
PubMed ID28735680
PubMed Central IDPMC5630127
Grant ListR01 GM086537 / GM / NIGMS NIH HHS / United States
R01 GM107103 / GM / NIGMS NIH HHS / United States