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Related Concept Videos

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Before a cell can divide, it must accurately replicate all of its chromosomes, including the DNA and its associated histone and non-histone proteins.  This process begins at numerous origins of replication during the S phase of the cell cycle in each of a cell’s chromosomes simultaneously. Certain nucleotides can act as origins of replication, but these sequences are not well defined - especially in complex, multi-cellular, eukaryotic species. The length of DNA that spans an origin...
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DNA replication has three main steps: initiation, elongation, and termination. Replication in prokaryotes begins when initiator proteins bind to the single origin of replication (ori) on the cell's circular chromosome. Replication then proceeds around the entire circle of the chromosome in each direction from the two replication forks, resulting in two DNA molecules.
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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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Profiling DNA Replication Timing Using Zebrafish as an In Vivo Model System
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Single-cell replication profiling to measure stochastic variation in mammalian replication timing.

Vishnu Dileep1, David M Gilbert2

  • 1Department of Biological Science, Florida State University, 319 Stadium Drive, Tallahassee, FL, 32306, USA.

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|February 1, 2018
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Summary

Replication timing variation in mouse cells is conserved across the genome, occurring stochastically and independently of factors dictating timing or environmental influences. This DNA replication pattern is consistent within cells and across homologous chromosomes.

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Area of Science:

  • Cellular and Molecular Biology
  • Genomics
  • Epigenetics

Background:

  • Mammalian DNA replication occurs in a temporal order during S-phase, linked to chromatin states.
  • Replication origins are chosen stochastically, but the variation in replication timing remains unclear.

Purpose of the Study:

  • To develop a method for measuring replication timing variation in single mouse embryonic stem cells.
  • To investigate the extent and characteristics of stochastic variation in DNA replication timing.

Main Methods:

  • Utilized DNA copy number analysis in single mouse embryonic stem cells.
  • Measured variations in replication timing across the genome.

Main Results:

  • Identified conserved borders between replicated and unreplicated DNA, defining nuclear compartments.
  • Observed that 50% of replication events varied by ±15% of S phase from their average timing.
  • Found this variation to be consistent across cells, homologous chromosomes, and genomic domains.

Conclusions:

  • Stochastic variation in DNA replication timing is a fundamental characteristic of mammalian cells.
  • Replication timing variation is independent of the elements that determine timing and external environmental factors.