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Profiling DNA Replication Timing Using Zebrafish as an In Vivo Model System
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DNA template strand segregation in developing zebrafish.

Stella M K Glasauer1, Therese Triemer2, Anne B Neef2

  • 1Department of Chemistry, University of Zurich, 8057 Zurich, Switzerland; Neuroscience Research Institute and Department of Molecular, Cellular and Developmental Biology, University of California Santa Barbara, Santa Barbara CA 93106, USA.

Cell Chemical Biology
|September 30, 2021
PubMed
Summary
This summary is machine-generated.

Asymmetric DNA inheritance was studied in zebrafish development. Researchers found no evidence supporting the immortal strand hypothesis, suggesting it doesn't prevent mutation accumulation in stem cells.

Keywords:
DNA metabolic labelingazide-alkyne "click" cycloadditioncell divisiondevelopmental biologyeye developmentfluorescence microscopystem cells

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Area of Science:

  • Developmental Biology
  • Cell Biology
  • Genetics

Background:

  • The immortal strand hypothesis proposes asymmetric DNA segregation to minimize mutations in stem cells.
  • This hypothesis links sister chromatid inheritance to daughter cell fates.

Purpose of the Study:

  • To investigate DNA template strand segregation during zebrafish development.
  • To test the immortal strand hypothesis in vivo using live imaging.

Main Methods:

  • Utilized (2'S)-2'-deoxy-2'-fluoro-5-ethynyluridine (F-ara-EdU) and bromodeoxyuridine (BrdU) for DNA labeling.
  • Employed light sheet microscopy for high-resolution, whole-embryo imaging of DNA segregation in zebrafish.
  • Tracked embryonic DNA dynamics throughout larval development in key stem cell niches.

Main Results:

  • Observed rapid depletion of older DNA template strands from stem cell niches (retina, brain, intestine) during larval development.
  • Identified prolonged label retention in quiescent progenitors that re-enter replication later.
  • Found no evidence of asymmetric template strand segregation in over 100 observed daughter cell pairs.

Conclusions:

  • Asymmetric DNA segregation, as predicted by the immortal strand hypothesis, does not appear to occur in developing zebrafish.
  • The hypothesis that asymmetric segregation minimizes mutational burden in stem cells is unlikely to apply to zebrafish development based on these findings.