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Related Concept Videos

Replication in Eukaryotes01:29

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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.
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In eukaryotic DNA replication, a single-stranded DNA fragment remains at the end of a chromosome after the removal of the final primer. This section of DNA cannot be replicated in the same manner as the rest of the strand because there is no 3’ end to which the newly synthesized DNA can attach. This non-replicated fragment results in gradual loss of the chromosomal DNA during each cell duplication. Additionally, it can induce a DNA damage response by enzymes that recognize single-stranded...
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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...
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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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Telomere Replication: Solving Multiple End Replication Problems.

Erin Bonnell1, Emeline Pasquier1, Raymund J Wellinger1

  • 1Department of Microbiology and Infectious Diseases, Faculty of Medicine and Health Sciences, Cancer Research Pavilion, Université de Sherbrooke, Sherbrooke, QC, Canada.

Frontiers in Cell and Developmental Biology
|April 19, 2021
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Summary
This summary is machine-generated.

Replication forks struggle to copy telomeres, the protective caps on chromosomes. Conserved mechanisms in yeast and mammals help overcome these challenges to maintain genomic stability.

Keywords:
DNA replicationgenome stabilityreplication fork stabilitytelomerestelomeric chromatin

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Area of Science:

  • Genetics
  • Molecular Biology
  • Cell Biology

Background:

  • Eukaryotic genomes are protected by telomeres, specialized nucleoprotein structures at chromosome ends.
  • Telomere replication is challenging due to repetitive DNA, a single-stranded 3' overhang, and secondary structures.
  • The end replication problem leads to telomere shortening, counteracted by telomerase, but conventional replication machinery handles most of telomere synthesis.

Purpose of the Study:

  • To review the challenges of replication fork progression through telomeres.
  • To highlight conserved mechanisms that maintain telomere integrity during replication in various organisms.
  • To emphasize the importance of overcoming replication obstacles for genomic stability.

Main Methods:

  • Review of existing literature on telomere replication and fork progression.
  • Comparative analysis of mechanisms in fission yeast, budding yeast, and mammals.
  • Focus on factors preventing or resolving replication fork stalling at telomeres.

Main Results:

  • Telomeric sequences, secondary structures, bound proteins, and t-loops impede replication fork passage.
  • Replication fork stalling at telomeres can lead to collapse and DNA breaks, compromising genomic stability.
  • Multiple conserved mechanisms exist to prevent stalling or promote restart of stalled forks at telomeres.

Conclusions:

  • Efficient telomere replication requires overcoming significant obstacles to prevent genomic instability.
  • Conserved mechanisms across species ensure telomere integrity during DNA replication.
  • Understanding these mechanisms is crucial for maintaining a stable genome.