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Related Concept Videos

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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S-Cdk Initiates DNA Replication02:38

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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).
Two states at the origin of replication
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Restarting Stalled Replication Forks02:37

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DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
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Chromosome Replication02:31

Chromosome Replication

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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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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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DNA Damage can Stall the Cell Cycle02:37

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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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Updated: Jun 22, 2025

Genome-wide Determination of Mammalian Replication Timing by DNA Content Measurement
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Genome-wide Determination of Mammalian Replication Timing by DNA Content Measurement

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DNA replication initiation timing is important for maintaining genome integrity.

Tristan T Reed1, Abigail H Kendal1, Katherine J Wozniak1,2

  • 1Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109.

Biorxiv : the Preprint Server for Biology
|July 1, 2024
PubMed
Summary
This summary is machine-generated.

DNA replication initiation in Bacillus subtilis is tightly controlled. Both under-initiation and over-initiation of DNA replication lead to increased sensitivity to genotoxic stress, impacting genome stability.

Keywords:
Bacillus subtilisCcrZDNA replicationDnaARecA

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Area of Science:

  • Microbiology
  • Molecular Biology
  • Genetics

Background:

  • DNA replication initiation is a critical process regulated by various factors.
  • In Bacillus subtilis, YabA acts as a negative regulator, while CcrZ kinase positively regulates replication initiation.
  • The impact of altered DNA replication initiation on genome stability is not fully understood.

Purpose of the Study:

  • To investigate the consequences of DNA replication under-initiation and over-initiation on genome stability in Bacillus subtilis.
  • To determine the relationship between replication initiation frequency and sensitivity to genotoxic stress.

Main Methods:

  • Measuring origin to terminus ratios as a proxy for replication initiation activity.
  • Assessing replication fork stress using RecA-GFP foci formation.
  • Evaluating sensitivity to genotoxic stress (mitomycin C) in strains with altered replication initiation.

Main Results:

  • ΔccrZ mutants and certain ccrZ alleles exhibited under-initiation of DNA replication.
  • yabA deletion or CcrZ overproduction resulted in over-initiation of DNA replication.
  • Cells with altered replication initiation frequencies, both under- and over-initiating, showed increased sensitivity to genotoxic stress.

Conclusions:

  • Under-initiation of DNA replication may lead to sensitivity to DNA damage due to insufficient DNA for homologous recombination repair.
  • Over-initiation of DNA replication causes replication fork stress, which is worsened by DNA damage.
  • Tight control of DNA replication initiation frequency is essential for maintaining genome stability and efficient DNA repair.