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Related Concept Videos

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...
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...
DNA Topoisomerases02:02

DNA Topoisomerases

Topoisomerases are enzymes that relax overwound DNA molecules during various cell processes, including DNA replication and transcription. These enzymes regulate positive and negative DNA supercoiling without changing the nucleotide sequence. DNA overwinding in a clockwise direction results in positively supercoiled DNA, whereas underwinding in a counterclockwise direction produces negatively supercoiled DNA.
Types and Mechanism of action
Topoisomerases are divided into two main types.  Type I...
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

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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FET proteins and PARylation-dependent condensates promote replication fork reversal and genome stability.

Nature communications·2026
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Distinct repair outcomes from single and convergent replication fork collapse.

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REPLAY: A reproducible and user-friendly application for DNA replication timing analysis from Repli-seq data.

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Related Experiment Video

Updated: May 21, 2026

Quantifying Replication Stress in Ovarian Cancer Cells Using Single-Stranded DNA Immunofluorescence
06:25

Quantifying Replication Stress in Ovarian Cancer Cells Using Single-Stranded DNA Immunofluorescence

Published on: February 10, 2023

Topological stress regulates replication fork dynamics in unperturbed S phase.

Deepika Jayaprakash1, Josie Gannon Patterson1, Ruthie Mulvaney1

  • 1Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USA.

Nature Communications
|May 19, 2026
PubMed
Summary

Topoisomerase IIA (TOP2A) is crucial for regulating DNA replication fork speed during early S-phase. Low TOP2A levels cause replication stress, while its overexpression enhances fork speed and suppresses cancer-related replication stress.

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Inducing a Site Specific Replication Blockage in E. coli Using a Fluorescent Repressor Operator System
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Inducing a Site Specific Replication Blockage in E. coli Using a Fluorescent Repressor Operator System

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

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Last Updated: May 21, 2026

Quantifying Replication Stress in Ovarian Cancer Cells Using Single-Stranded DNA Immunofluorescence
06:25

Quantifying Replication Stress in Ovarian Cancer Cells Using Single-Stranded DNA Immunofluorescence

Published on: February 10, 2023

Inducing a Site Specific Replication Blockage in E. coli Using a Fluorescent Repressor Operator System
11:19

Inducing a Site Specific Replication Blockage in E. coli Using a Fluorescent Repressor Operator System

Published on: August 21, 2016

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

Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • Accurate genome duplication is essential for cell viability.
  • Replication fork progression requires tight regulation.
  • Disruptions in DNA replication contribute to genomic instability.

Purpose of the Study:

  • To elucidate the mechanisms controlling replication fork dynamics during unperturbed S-phase.
  • To investigate the role of Topoisomerase IIA (TOP2A) in regulating replication fork speed.
  • To understand the link between TOP2A, torsional stress, and DNA replication stress.

Main Methods:

  • Analysis of replication fork elongation rates in early and late S-phase.
  • Investigating the impact of TOP2A levels on replication fork dynamics.
  • Assessing ATR-CHK1 signaling activation under varying TOP2A conditions.
  • Evaluating the effect of TOP2A overexpression on oncogene-induced replication stress.

Main Results:

  • Replication forks elongate slower in early S-phase and faster in late S-phase.
  • Elevated origin firing and low TOP2A in early S-phase induce torsional stress, leading to replisome uncoupling and reduced fork speed.
  • TOP2A overexpression enhances fork speed and mitigates replication stress in early S-phase.
  • TOP2A overexpression suppresses oncogene-driven replication stress.

Conclusions:

  • TOP2A acts as a limiting replication factor during unperturbed early S-phase.
  • Basal ATR-CHK1 signaling is triggered by transient replisome uncoupling.
  • TOP2A upregulation in cancer may serve as a compensatory mechanism against oncogene-induced replication stress.
  • TOP2A is a key regulator of replication fork dynamics.