Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Restarting Stalled Replication Forks02:37

Restarting Stalled Replication Forks

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, a...
Restarting Stalled Replication Forks02:37

Restarting Stalled Replication Forks

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, a...
S-Cdk Initiates DNA Replication02:38

S-Cdk Initiates DNA Replication

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
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of replication.
S-Cdk Initiates DNA Replication02:38

S-Cdk Initiates DNA Replication

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
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of replication.
The DNA Replication Fork01:02

The DNA Replication Fork

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 forks, one in...
The DNA Replication Fork01:02

The DNA Replication Fork

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 forks, one in...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Targeting NFATc1-regulated MTHFD2 one-carbon metabolism to suppress sustained T-cell-mediated inflammation in rheumatoid arthritis.

Signal transduction and targeted therapy·2026
Same author

Structural basis for uracil removal from DNA by human SMUG1.

Nature communications·2026
Same author

TGF-α/EGFR-mediated lymphatic metastasis reveals a repositionable therapeutic target in breast cancer.

NPJ breast cancer·2026
Same author

A monofunctional-like mutant of DNA glycosylase NTHL1 changes the dynamics of DNA repair during acute oxidative stress.

The Journal of biological chemistry·2026
Same author

Emerging roles of RNA:DNA hybrid regulation by mammalian ribonuclease H2 in replication stress and cancer.

Journal of cell science·2025
Same author

Nucleobase catalysts for the enzymatic activation of 8-oxoguanine DNA glycosylase 1.

RSC chemical biology·2025
Same journal

In This Issue.

Proceedings of the National Academy of Sciences of the United States of America·2026
Same journal

Long-term cultural continuity across the Neanderthal-modern human sequence at Üçağızlı II Cave, northern Levant.

Proceedings of the National Academy of Sciences of the United States of America·2026
Same journal

Dolphins use names to remember whom to avoid.

Proceedings of the National Academy of Sciences of the United States of America·2026
Same journal

Retraction for Shaked and Frenkel, Curiouser and curiouser: Meningeal lymphoid structures in the aging brain.

Proceedings of the National Academy of Sciences of the United States of America·2026
Same journal

Small but mighty: The outsized role of small water bodies in the global carbon cycle.

Proceedings of the National Academy of Sciences of the United States of America·2026
Same journal

Functional traits produce conditional outcomes in different community contexts.

Proceedings of the National Academy of Sciences of the United States of America·2026
See all related articles

Related Experiment Video

Updated: Jun 9, 2026

Direct Restart of a Replication Fork Stalled by a Head-On RNA Polymerase
07:27

Direct Restart of a Replication Fork Stalled by a Head-On RNA Polymerase

Published on: April 29, 2010

Chk1 promotes replication fork progression by controlling replication initiation.

Eva Petermann1, Mick Woodcock, Thomas Helleday

  • 1Gray Institute for Radiation Oncology and Biology, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, United Kingdom. e.petermann@bham.ac.uk

Proceedings of the National Academy of Sciences of the United States of America
|September 1, 2010
PubMed
Summary
This summary is machine-generated.

Checkpoint kinase 1 (Chk1) normally suppresses DNA replication origins. Inhibiting origin firing in Chk1-deficient cells rescues slow replication fork speeds, revealing Chk1

More Related Videos

Strand-Specific Analysis of Proteins at Replicating DNA Strands by Enrichment and Sequencing of Protein-Associated Nascent DNA Method
08:53

Strand-Specific Analysis of Proteins at Replicating DNA Strands by Enrichment and Sequencing of Protein-Associated Nascent DNA Method

Published on: May 2, 2025

Visualization of DNA Replication in the Vertebrate Model System DT40 using the DNA Fiber Technique
07:18

Visualization of DNA Replication in the Vertebrate Model System DT40 using the DNA Fiber Technique

Published on: October 27, 2011

Related Experiment Videos

Last Updated: Jun 9, 2026

Direct Restart of a Replication Fork Stalled by a Head-On RNA Polymerase
07:27

Direct Restart of a Replication Fork Stalled by a Head-On RNA Polymerase

Published on: April 29, 2010

Strand-Specific Analysis of Proteins at Replicating DNA Strands by Enrichment and Sequencing of Protein-Associated Nascent DNA Method
08:53

Strand-Specific Analysis of Proteins at Replicating DNA Strands by Enrichment and Sequencing of Protein-Associated Nascent DNA Method

Published on: May 2, 2025

Visualization of DNA Replication in the Vertebrate Model System DT40 using the DNA Fiber Technique
07:18

Visualization of DNA Replication in the Vertebrate Model System DT40 using the DNA Fiber Technique

Published on: October 27, 2011

Area of Science:

  • Molecular Biology
  • Cell Cycle Regulation
  • DNA Replication

Background:

  • DNA replication initiates at specific replication origins.
  • Metazoan cells possess numerous potential origins, but only a subset are activated per S phase.
  • The ATR-Chk1 pathway regulates origin firing, suppressing it during replication stress and normal S phase via Cdk2 inhibition.

Purpose of the Study:

  • To investigate the causal link between increased origin firing and reduced replication fork progression.
  • To determine if inhibiting origin firing can rescue slow replication fork speeds in Chk1-deficient cells.

Main Methods:

  • Utilized the Cdk inhibitor roscovitine to block origin firing.
  • Employed RNA interference (RNAi) to deplete Cdc7, another regulator of origin firing.
  • Assessed replication fork progression rates in Chk1-inhibited or depleted cells under these conditions.

Main Results:

  • Inhibition of origin firing using roscovitine or Cdc7 depletion alleviated slow replication fork speeds in Chk1-deficient cells.
  • This indicates that increased origin firing is a cause of reduced replication fork progression.
  • Chk1 activity is crucial for maintaining normal replication fork speeds during S phase.

Conclusions:

  • Increased replication initiation (origin firing) directly leads to slower replication fork progression.
  • The ATR-Chk1 pathway promotes efficient replication fork progression in normal S phase by controlling origin activity.
  • Findings elucidate a critical mechanism for coordinating origin firing and fork progression during DNA replication.