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.
journal_name
Dev Celljournal_title
Developmental cellauthors
Song Y,Marmion RA,Park JO,Biswas D,Rabinowitz JD,Shvartsman SYdoi
10.1016/j.devcel.2017.06.013subject
Has Abstractpub_date
2017-08-07 00:00:00pages
301-308.e3issue
3eissn
1534-5807issn
1878-1551pii
S1534-5807(17)30501-4journal_volume
42pub_type
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