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Telomeres and Telomerase02:41

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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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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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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...
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The double-stranded structure of DNA has two major advantages. First, it serves as a safe repository of genetic information where one strand serves as the back-up in case the other strand is damaged. Second, the double-helical structure can be wrapped around proteins called histones to form nucleosomes, which can then be tightly wound to form chromosomes. This way, DNA chains up to 2 inches long can be contained within microscopic structures in a cell. A double-stranded break not only damages...
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A functional eukaryotic chromosome must contain three elements: a centromere, telomeres, and numerous origins of replication.
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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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Challenging endings: How telomeres prevent fragility.

Galina Glousker1, Joachim Lingner1

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Telomere replication challenges arise from noncanonical DNA structures. Fragile telomeres result from DNA repair processes, not direct replication insults, impacting various diseases.

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Area of Science:

  • Genetics and Molecular Biology
  • Cell Biology

Background:

  • Telomere replication is complex, facing obstacles from noncanonical nucleic acid structures.
  • Replication stress at telomeres leads to fragile telomeres with abnormal chromosome appearance.

Purpose of the Study:

  • To review and hypothesize the molecular mechanisms underlying telomere fragility.
  • To explore the role of DNA repair in telomere fragility.

Main Methods:

  • Review of existing literature on telomere replication, DNA repair, and fragile telomeres.
  • Hypothesis formulation based on current understanding of molecular processes.

Main Results:

  • Telomere fragility is proposed to be a secondary consequence of DNA repair of damaged replication forks.
  • Homologous DNA recombination machinery plays a key role in this process.
  • Incomplete DNA synthesis and partial chromatin condensation contribute to observed fragility.

Conclusions:

  • Telomere fragility is a complex phenomenon linked to DNA repair pathways, particularly homologous recombination.
  • This fragility is exacerbated in various disease conditions, highlighting its clinical relevance.