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Related Concept Videos

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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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

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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).
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S-Cdk Initiates DNA Replication02:38

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Regulating post-translational modifications of the eukaryotic replication clamp PCNA.

Helle D Ulrich1

  • 1Cancer Research UK London Research Institute, Clare Hall Laboratories, Blanche Lane, South Mimms, EN6 3LD, United Kingdom. helle.ulrich@cancer.org.uk

DNA Repair
|February 17, 2009
PubMed
Summary

Ubiquitin and SUMO modifications of proliferating cell nuclear antigen (PCNA) regulate DNA repair pathways during replication. This review details the regulatory mechanisms controlling PCNA modifications, emphasizing DNA template roles.

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Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Proliferating cell nuclear antigen (PCNA) is a eukaryotic sliding clamp crucial for DNA replication and repair.
  • PCNA undergoes post-translational modifications, including ubiquitylation and SUMOylation, which dictate DNA lesion processing pathways.
  • These modifications are critical for maintaining genome stability during DNA replication stress.

Purpose of the Study:

  • To review the regulatory mechanisms controlling PCNA ubiquitylation and SUMOylation.
  • To highlight the role of the DNA template in activating PCNA modification factors.
  • To compare regulatory similarities and variations across different organisms.

Main Methods:

  • Literature review of recent studies on PCNA modifications.
  • Analysis of molecular mechanisms governing ubiquitylation and SUMOylation.
  • Comparative analysis of regulatory pathways in various eukaryotic organisms.

Main Results:

  • Detailed understanding of how ubiquitylation and SUMOylation alter PCNA properties.
  • Identification of cellular signals that trigger specific PCNA modifications.
  • Emphasis on the DNA template's role in recruiting and activating conjugation factors.

Conclusions:

  • PCNA modifications are tightly regulated to ensure appropriate DNA repair pathway choice.
  • The DNA template is a key determinant in orchestrating PCNA ubiquitylation and SUMOylation.
  • Conserved and divergent mechanisms regulate PCNA modifications across eukaryotes.