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Related Concept Videos

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...
Homologous Recombination02:31

Homologous Recombination

The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
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...
Replicative Cell Senescence02:15

Replicative Cell Senescence

Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds the telomeric...
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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Related Experiment Video

Updated: Jun 24, 2026

In Vitro Directed Evolution of a Restriction Endonuclease with More Stringent Specificity
09:16

In Vitro Directed Evolution of a Restriction Endonuclease with More Stringent Specificity

Published on: March 25, 2020

Cyclin-dependent kinases prevent DNA re-replication through multiple mechanisms.

V Q Nguyen1, C Co, J J Li

  • 1Department of Biochemistry and Biophysics, University of California, San Francisco 94143-0414, USA.

Nature
|June 29, 2001
PubMed
Summary
This summary is machine-generated.

Preventing DNA replication re-initiation is crucial for cell cycle control. In yeast, B-type cyclin-dependent kinases (CDKs) use three mechanisms to block re-replication, ensuring genome stability.

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Last Updated: Jun 24, 2026

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Published on: March 25, 2020

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Assessment of Global DNA Double-Strand End Resection using BrdU-DNA Labeling coupled with Cell Cycle Discrimination Imaging
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Assessment of Global DNA Double-Strand End Resection using BrdU-DNA Labeling coupled with Cell Cycle Discrimination Imaging

Published on: April 28, 2021

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • Faithful genome replication once per cell cycle is essential for genetic stability.
  • Eukaryotic DNA replication initiates at multiple origins, which must be prevented from re-initiating within the same cell cycle.
  • Cyclin-dependent kinases (CDKs) are known to play a role in blocking replication re-initiation, but the precise mechanisms remain elusive.

Purpose of the Study:

  • To elucidate the mechanisms by which B-type cyclin-dependent kinases (CDKs) prevent DNA replication re-initiation in Saccharomyces cerevisiae.
  • To determine the functional importance of individual inhibitory pathways regulated by CDKs.

Main Methods:

  • Investigated the role of B-type CDKs in preventing replication re-initiation in yeast.
  • Analyzed the effects of CDK activity on origin recognition complex (ORC) phosphorylation, Cdc6 activity, and Mcm2-7 complex localization.
  • Assessed the consequences of disrupting these regulatory pathways on DNA replication in G2/M phase cells.

Main Results:

  • B-type CDKs in Saccharomyces cerevisiae employ multiple, overlapping mechanisms to inhibit replication re-initiation.
  • These mechanisms include phosphorylation of the origin recognition complex (ORC), downregulation of Cdc6 activity, and nuclear exclusion of the Mcm2-7 complex.
  • Only when all three inhibitory pathways are simultaneously disrupted do replication origins re-initiate DNA replication in G2/M cells.

Conclusions:

  • B-type CDKs utilize a multi-pronged inhibitory strategy to ensure a single round of DNA replication per cell cycle.
  • Each of the identified regulatory mechanisms (ORC phosphorylation, Cdc6 downregulation, Mcm2-7 exclusion) is functionally significant in preventing re-initiation.
  • These findings provide a comprehensive understanding of how eukaryotic cells maintain genome stability by strictly controlling DNA replication.