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Related Concept Videos

Replication in Eukaryotes01:29

Replication in Eukaryotes

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In eukaryotic cells, DNA replication is highly conserved and tightly regulated. Multiple linear chromosomes must be duplicated with high fidelity before cell division, so there are many proteins that fulfill specialized roles in the replication process. Replication occurs in three phases: initiation, elongation, and termination, and ends with two complete sets of chromosomes in the nucleus.
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The DNA Replication Fork01:02

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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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In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
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Replication in Prokaryotes01:32

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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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The cell cycle is a series of events leading to DNA duplication followed by the division of cell content to form two daughter cells. The cell cycle progresses in four stages—the cell increases in size (gap 1 or G1-phase), duplicates its DNA (synthesis or S-phase), prepares to divide (gap 2 or G2-phase), and divides (mitosis or M-phase).
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DNA replication is a well-evolved process that copies millions of base pairs with high fidelity during each cell division. Occasionally a wrong base or a long stretch of wrong bases may get added to the daughter strands. If the errors are left unchecked, cells might accumulate several mutations that might endanger their  survival. Therefore, the copying errors are checked and repaired at three levels.
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Genome-wide Determination of Mammalian Replication Timing by DNA Content Measurement
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Embryonic genome instability upon DNA replication timing program emergence.

Saori Takahashi1, Hirohisa Kyogoku2,3, Takuya Hayakawa4

  • 1Laboratory for Developmental Epigenetics, RIKEN Center for Biosystems Dynamics Research (BDR), Kobe, Japan.

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|August 28, 2024
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Summary
This summary is machine-generated.

Early mouse embryos show a temporary period of genomic instability due to uncoordinated DNA replication. This instability, marked by slow replication forks and DNA damage, is resolved by the 8-cell stage, ensuring genome integrity.

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G2-seq: A High Throughput Sequencing-based Technique for Identifying Late Replicating Regions of the Genome
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Area of Science:

  • Developmental Biology
  • Genetics
  • Molecular Biology

Background:

  • Faithful DNA replication is crucial for maintaining genome integrity.
  • Replication defects and chromosome segregation errors are observed in early embryogenesis.
  • Regulation of DNA replication in early mammalian embryos is not well understood.

Purpose of the Study:

  • To investigate the DNA replication program in pre-implantation mouse embryos at a single-cell level.
  • To identify critical periods of genomic instability during early development.
  • To understand the coordination between replication timing and fork progression.

Main Methods:

  • Construction of a single-cell, genome-wide DNA replication atlas in mouse embryos.
  • Analysis of replication timing programs and replication fork speeds.
  • Assessment of replication stress, DNA damage, and chromosome segregation errors.

Main Results:

  • Early embryos (1-2 cell) lack a replication timing program with slow, uniform replication.
  • A somatic-like replication program initiates by the 4-cell stage, but with slow forks and increased replication stress.
  • Break-type chromosome segregation errors occur during the 4-to-8 cell division, linked to late-replicating regions.
  • Nucleoside supplementation rescues errors by accelerating fork speed and reducing stress.
  • By the 8-cell stage, replication dynamics normalize, and chromosome aberrations decrease.

Conclusions:

  • A transient period of genomic instability occurs during normal mouse development.
  • This instability is linked to a lack of coordination between replication timing and fork regulation in early S phase.
  • Coordination of replication processes is vital for maintaining genome stability during embryogenesis.