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Related Concept Videos

Telomeres and Telomerase02:41

Telomeres and Telomerase

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 DNA.
Telomeres and Telomerase02:41

Telomeres and Telomerase

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 DNA.
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...
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...
Replication in Eukaryotes01:29

Replication in Eukaryotes

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
Eukaryotic replication follows many of the same...
Replication in Eukaryotes02:31

Replication in Eukaryotes

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Analyzing Telomeric Protein-DNA Interactions Using Single-Molecule Magnetic Tweezers
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Published on: August 30, 2024

Multiple pathways inhibit NHEJ at telomeres.

Stéphane Marcand1, Benjamin Pardo, Ariane Gratias

  • 1Centre National de la Recherche Scientifque UMR 217, Institut de Radiobiologie Cellulaire et Moléculaire, CEA/Fontenay, 92265 Fontenay-aux-roses cedex, France. stephane.marcand@cea.fr

Genes & Development
|May 3, 2008
PubMed
Summary

The Rap1 protein prevents telomere fusions in yeast by inhibiting the nonhomologous end-joining (NHEJ) pathway through multiple independent mechanisms involving Rif2 and Sir4 proteins.

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Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • Telomeres protect chromosome ends from fusion.
  • The nonhomologous end-joining (NHEJ) pathway is a major DNA repair mechanism.
  • Inhibition of NHEJ at telomeres is crucial for genome stability.

Purpose of the Study:

  • To investigate the mechanisms by which Rap1 inhibits NHEJ at telomeres in Saccharomyces cerevisiae.
  • To identify the specific domains and protein interactions involved in Rap1-mediated NHEJ inhibition.

Main Methods:

  • Yeast genetics
  • Protein interaction studies
  • Telomere function assays

Main Results:

  • Rap1 inhibits NHEJ through two parallel pathways involving Rif2 and Sir4 via its C-terminal domain.
  • Rap1's central domain independently inhibits NHEJ, separate from Rif2 and Sir4.
  • Rap1 utilizes multiple distinct pathways to prevent telomere fusions.

Conclusions:

  • Rap1 is a key regulator of telomere integrity, employing diverse inhibitory strategies.
  • The findings provide insights into Rif2 multifunctionality and its evolutionary origins from ORC subunits.