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Related Concept Videos

Restarting Stalled Replication Forks02:37

Restarting Stalled Replication Forks

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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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The DNA Replication Fork01:02

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An organism’s genome needs to be duplicated in an efficient and error-free manner for its growth and survival. The replication fork is a Y-shaped active region where two strands of DNA are separated and replicated continuously. The coupling of DNA unzipping and complementary strand synthesis is a characteristic feature of a replication fork.   Organisms with small circular DNA, such as E. coli, often have a single origin of replication; therefore, they have only two replication...
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The DNA Replication Fork01:02

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Replication in Eukaryotes01:29

Replication in Eukaryotes

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In eukaryotic cells, DNA replication is highly conserved and tightly regulated. Multiple linear chromosomes must be duplicated with high fidelity before cell division, so there are many proteins that fulfill specialized roles in the replication process. Replication occurs in three phases: initiation, elongation, and termination, and ends with two complete sets of chromosomes in the nucleus.
Many Proteins Orchestrate Replication at the Origin
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Replication in Eukaryotes02:31

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Related Experiment Video

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Direct Restart of a Replication Fork Stalled by a Head-On RNA Polymerase
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Replication fork reversal in eukaryotes: from dead end to dynamic response.

Kai J Neelsen1, Massimo Lopes2

  • 11] Institute of Molecular Cancer Research, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland. [2] The Novo Nordisk Foundation Center for Protein Research, 2200 Copenhagen, Denmark.

Nature Reviews. Molecular Cell Biology
|February 26, 2015
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Summary

Replication fork reversal, a DNA repair mechanism, is now understood as a conserved, regulated process in eukaryotes. This finding has significant implications for maintaining genome stability and developing cancer therapies.

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Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • Replication fork reversal, a process where replication forks remodel into four-way junctions, was hypothesized to aid DNA damage tolerance and repair.
  • Historically, in vivo evidence for fork reversal was limited to prokaryotes and specific yeast mutants, questioning its evolutionary conservation and physiological importance.
  • Recent advancements in visualizing replication forks in metazoans have revealed fork reversal as a widespread, reversible, and regulated cellular mechanism.

Purpose of the Study:

  • To investigate the physiological relevance and evolutionary conservation of replication fork reversal in eukaryotes.
  • To explore the implications of fork reversal for replication completion, chromosome integrity, and the DNA damage response.
  • To identify and study eukaryotic factors involved in fork remodelling for insights into genome maintenance.

Main Methods:

  • Visualization of replication forks in metazoan cells.
  • Analysis of DNA damage tolerance and repair pathways.
  • Identification and functional characterization of eukaryotic factors involved in fork remodelling.

Main Results:

  • Fork reversal is a global, reversible, and regulated process in metazoans.
  • This process plays a crucial role in replication completion and maintaining chromosome integrity.
  • Fork reversal is integral to the cell's DNA damage response.

Conclusions:

  • Replication fork reversal is an evolutionarily conserved and physiologically relevant mechanism in eukaryotes.
  • Understanding eukaryotic fork remodelling factors offers new insights into genome maintenance.
  • These factors represent potential therapeutic targets for cancer treatment.