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S-Cdk Initiates DNA Replication

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 Replication

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.

Restarting Stalled Replication Forks

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 Damage can Stall the Cell Cycle

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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...

DNA Damage Can Stall the Cell Cycle

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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...

The Cell Cycle Control System

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The cell cycle is an organized set of events that leads the cell to divide into two daughter cells, each containing chromosomes identical to the parent cell. It is the cell cycle that leads to the formation of an entire organism from a single-cell zygote. Besides, cell division also functions in the renewal or repair of tissues in adult multicellular eukaryotes. For example, in the bone marrow, the stem cells divide to form new blood cells. Although essential for several functions, cell...

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Related Experiment Video

Updated: Jul 2, 2026

Temporal Tracking of Cell Cycle Progression Using Flow Cytometry without the Need for Synchronization

Temporal Tracking of Cell Cycle Progression Using Flow Cytometry without the Need for Synchronization

Published on: August 16, 2015

Cell cycle progression requires the CDC-48UFD-1/NPL-4 complex for efficient DNA replication.

Julien Mouysset¹, Alexandra Deichsel, Sandra Moser

¹Centre for Molecular Neurobiology (ZMNH), University of Hamburg, Falkenried 94, 20251 Hamburg, Germany.

Proceedings of the National Academy of Sciences of the United States of America

|August 30, 2008

Summary

The chaperone ATPase CDC-48 is crucial for DNA replication and cell cycle control in C. elegans. Its depletion causes developmental defects due to replication stress and checkpoint activation.

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Area of Science:

Cell Biology
Genetics
Molecular Biology

Background:

The role of the chaperone ATPase Cdc48/p97 in cell division has been unclear since its initial discovery in yeast cell division cycle (cdc) mutants.
Genetic screens in yeast identified cdc48 mutants, but their specific function during cell division remained elusive.

Purpose of the Study:

To investigate the function of Caenorhabditis elegans CDC-48 in DNA replication and cell cycle control.
To elucidate the role of the CDC-48(UFD-1/NPL-4) complex in embryonic and germline development.

Main Methods:

Genetic analysis of CDC-48, UFD-1, and NPL-4 in Caenorhabditis elegans.
Assessment of S phase progression, DNA replication, DNA content, and response to replication-blocking agents.
Investigation of DNA replication checkpoint activation.

Main Results:

Caenorhabditis elegans CDC-48 has an unanticipated role in DNA replication linked to cell cycle control.
Depletion of CDC-48, UFD-1, or NPL-4 leads to S phase progression defects and activation of the DNA replication checkpoint.
Reduced DNA content, decreased DNA synthesis, and hypersensitivity to replication inhibitors were observed in depleted worms.

Conclusions:

The CDC-48(UFD-1/NPL-4) complex is essential for S phase progression in mitotic cells, impacting embryonic cell division and germline development.
Replication stress and subsequent checkpoint activation underlie the developmental defects observed upon CDC-48 complex depletion.
CDC-48(UFD-1/NPL-4) plays a vital role in maintaining genome stability and facilitating cell cycle progression through its function in DNA replication.