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S-Cdk Initiates DNA Replication02:38

S-Cdk Initiates DNA Replication

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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
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of...
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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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DNA Damage Can Stall the Cell Cycle02:36

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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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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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Restarting Stalled Replication Forks

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Negative Regulator Molecules01:23

Negative Regulator Molecules

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Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
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Related Experiment Video

Updated: Jan 4, 2026

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols
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Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols

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DNA replication and mitotic entry: A brake model for cell cycle progression.

Bennie Lemmens1, Arne Lindqvist2

  • 1Department of Medical Biochemistry and Biophysics, Karolinska Institutet and Science for Life Laboratory, Stockholm, Sweden arne.lindqvist@ki.se bennie.lemmens@ki.se.

The Journal of Cell Biology
|November 13, 2019
PubMed
Summary

DNA replication is crucial for cell cycle coordination, preventing genome instability. New models show DNA replication and molecular brakes regulate cyclin-dependent kinase (CDK) activation, timing cell division.

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • The cell cycle duplicates genomes and divides DNA, requiring precise coordination.
  • Incomplete DNA replication before cell division causes genome instability and cell death.

Purpose of the Study:

  • To redefine the coupling between DNA replication and cell division.
  • To present an updated cell cycle model for human cells incorporating new findings.

Main Methods:

  • Review of recent observations on DNA replication and cell cycle coordination.
  • Development of a new cell cycle model based on molecular brake release kinetics.

Main Results:

  • DNA replication actively coordinates cell cycle progression, not just follows it.
  • Checkpoint kinase signaling from DNA replication restricts cyclin-dependent kinase (CDK) activity.
  • The S/G2 transition is a key regulatory point for mitosis timing.

Conclusions:

  • Updated cell cycle model highlights DNA replication's regulatory role.
  • Model features a single trigger and sequential release of three molecular brakes.
  • This mechanism governs the kinetics of CDK activation and cell division timing.