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Dynamic Control of DNA Precursor Syn...
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Princeton University.
Dynamic Control of DNA Precursor Synthesis in Early Embryos.
紀錄類型:
書目-語言資料,手稿 : Monograph/item
正題名/作者:
Dynamic Control of DNA Precursor Synthesis in Early Embryos./
作者:
Song, Yonghyun.
面頁冊數:
1 online resource (70 pages)
附註:
Source: Dissertation Abstracts International, Volume: 79-05(E), Section: B.
Contained By:
Dissertation Abstracts International79-05B(E).
標題:
Molecular biology. -
電子資源:
click for full text (PQDT)
ISBN:
9780355480658
Dynamic Control of DNA Precursor Synthesis in Early Embryos.
Song, Yonghyun.
Dynamic Control of DNA Precursor Synthesis in Early Embryos.
- 1 online resource (70 pages)
Source: Dissertation Abstracts International, Volume: 79-05(E), Section: B.
Thesis (Ph.D.)
Includes bibliographical references
Animal embryogenesis starts with multiple rounds of nuclear divisions. During and shortly after these divisions, the zygotic genome is activated, the body plan of the organism is established, and gastrulation initiates the formation of tissues and organs. For these events to occur, the embryo needs to generate energy and provide metabolic precursors for biosynthesis. In this thesis, we used quantitative mass spectrometry and genetic manipulation techniques to examine how the early Drosophila melanogaster embryo controls the synthesis of DNA precursors.
Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2018
Mode of access: World Wide Web
ISBN: 9780355480658Subjects--Topical Terms:
583443
Molecular biology.
Index Terms--Genre/Form:
554714
Electronic books.
Dynamic Control of DNA Precursor Synthesis in Early Embryos.
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Adviser: Stanislav Y. Shvartsman.
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Princeton University
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Animal embryogenesis starts with multiple rounds of nuclear divisions. During and shortly after these divisions, the zygotic genome is activated, the body plan of the organism is established, and gastrulation initiates the formation of tissues and organs. For these events to occur, the embryo needs to generate energy and provide metabolic precursors for biosynthesis. In this thesis, we used quantitative mass spectrometry and genetic manipulation techniques to examine how the early Drosophila melanogaster embryo controls the synthesis of DNA precursors.
520
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Early Drosophila embryos undergo 13 rapid and synchronous nuclear division cycles within two hours of fertilization. This exponential increase in the number of nuclei requires massive amounts of deoxynucleoside triphosphates (dNTPs). 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 (RNR), is inhibited by endogenous levels of dATP present at fertilization and is activated as dATP is depleted via DNA polymerization. In the absence of inhibition by dATP, dNTP levels increase dramatically and induce embryonic lethality with particularly severe structural defects in the anterior regions.
520
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In conclusion, this thesis demonstrated that dNTP synthesis in early Drosophila embryos is controlled mainly through a single feedback inhibition loop at the end of the dNTP production pathway. In the process, we have also found that misregulation of RNR activity surprisingly confers tissue specific defects. Going forward, this thesis establishes Drosophila development as a platform for mechanistic and quantitative studies of dNTP metabolism.
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2018
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click for full text (PQDT)
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