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Related Concept Videos

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.
Chromosome Replication02:31

Chromosome Replication

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 of...
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...
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...
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...

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Combining Mitotic Cell Synchronization and High Resolution Confocal Microscopy to Study the Role of Multifunctional Cell Cycle Proteins During Mitosis
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Cdt1 and geminin in DNA replication initiation.

Christophe Caillat1, Anastassis Perrakis

  • 1Department of Biochemistry, Netherlands Cancer Institute, Plesmanlaan 121, 1066CX, Amsterdam, The Netherlands.

Sub-Cellular Biochemistry
|August 25, 2012
PubMed
Summary
This summary is machine-generated.

The Cdt1-Geminin complex acts as a molecular switch controlling DNA replication initiation. Structural studies reveal how this interaction ensures DNA is replicated only once per cell cycle.

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • DNA replication initiation is tightly regulated to ensure genomic stability.
  • Cdt1 promotes pre-replication complex assembly, while Geminin inhibits it.
  • The balance between Cdt1 and Geminin is crucial for cell cycle control.

Purpose of the Study:

  • To review structural studies of Cdt1 and Geminin.
  • To elucidate the molecular mechanism of the Cdt1-Geminin switch.
  • To understand how this switch ensures once-per-cell-cycle DNA replication.

Main Methods:

  • Structural biology techniques (e.g., X-ray crystallography, cryo-EM).
  • Biochemical assays to study protein-protein interactions.
  • Cell-based assays to assess DNA replication control.

Main Results:

  • Detailed structural insights into Cdt1-Geminin interactions.
  • Understanding of Geminin's inhibition of Cdt1 activity and stability.
  • Mechanism by which the complex regulates MCM loading onto ORC.

Conclusions:

  • The Cdt1-Geminin complex functions as a critical molecular switch for DNA replication.
  • Structural and functional studies provide a framework for understanding replication control.
  • This regulation is essential for preventing re-replication and maintaining genome integrity.