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DNA replication involves the separation of the two strands of the double helix, with each strand serving as a template from which the new complementary strand is copied.  After replication, each double-stranded DNA includes one parental or “old” strand and one “new” strand. This is known as semiconservative replication. The resulting DNA molecules have the same sequence and are divided equally into the two daughter cells.
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An organism’s genome needs to be duplicated in an efficient and error-free manner for its growth and survival. The replication fork is a Y-shaped active region where two strands of DNA are separated and replicated continuously. The coupling of DNA unzipping and complementary strand synthesis is a characteristic feature of a replication fork.   Organisms with small circular DNA, such as E. coli, often have a single origin of replication; therefore, they have only two replication...
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Profiling DNA Replication Timing Using Zebrafish as an In Vivo Model System
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DNA Replication Timing Enters the Single-Cell Era.

Ichiro Hiratani1, Saori Takahashi2

  • 1Laboratory for Developmental Epigenetics, RIKEN Center for Biosystems Dynamics Research (BDR), Kobe, Hyogo 650-0047, Japan. ichiro.hiratani@riken.jp.

Genes
|March 20, 2019
PubMed
Summary

Mammalian DNA replication timing occurs in megabase-sized domains. Recent single-cell profiling confirms these replication domains are preserved at the individual cell level, advancing genome regulation studies.

Keywords:
3D genome organizationDNA replication timingmammalian chromosomereplication domainsingle-cell Repli-seq (scRepli-seq)

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Area of Science:

  • Genomics
  • Molecular Biology
  • Cell Biology

Background:

  • DNA replication timing in mammalian cells is organized into megabase (Mb)-sized chromosomal domains.
  • Replication timing correlates with transcription, chromatin structure, and 3D genome organization.
  • Replication timing serves as a key entry point for exploring genome regulation.

Purpose of the Study:

  • To review current knowledge on DNA replication timing regulation in mammals based on population studies.
  • To outline findings from recent single-cell DNA replication profiling.
  • To discuss future directions and challenges in the field.

Main Methods:

  • Review of existing literature on cell population-based DNA replication timing studies.
  • Analysis of data from newly developed single-cell DNA replication profiling methods.
  • Comparative analysis of population-level versus single-cell replication domain data.

Main Results:

  • Mb-sized replication domains observed in population studies are well-preserved in individual mammalian cells.
  • Single-cell profiling validates the robustness of replication timing domains at the cellular level.
  • This validates the use of population-level data for understanding single-cell replication dynamics.

Conclusions:

  • Single-cell DNA replication profiling confirms the conservation of replication domains across individual mammalian cells.
  • This breakthrough validates previous population-based findings and opens new avenues for single-cell genomics research.
  • Future research should focus on leveraging single-cell data to further elucidate genome regulation mechanisms.