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Related Concept Videos

Long-patch Base Excision Repair01:02

Long-patch Base Excision Repair

Since the discovery of the two BER pathways, there has been a debate about how a cell chooses one pathway over the other and the factors determining this selection. Numerous in vitro experiments have pointed out multiple determinants for the sub-pathway selection. These are:
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...
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...
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.

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Related Experiment Video

Updated: May 11, 2026

Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer
08:34

Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer

Published on: April 13, 2015

Repair pathway choice at dysfunctional telomeres.

Abigail Gillespie1, Joe Nassour1

  • 1University of Colorado School of Medicine, 12801 E. 17th Ave, Aurora, CO 80045, USA.

Trends in Cell Biology
|May 9, 2026
PubMed
Summary
This summary is machine-generated.

Telomere crisis drives cancer genome evolution by causing replication defects. Mutagenic repair of short telomeres leads to chromosomal fusions and complex rearrangements in cancer.

Keywords:
DNA repairgenome instabilitymicrohomology-mediated end joiningreplication stresstelomere

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Last Updated: May 11, 2026

Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer
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Area of Science:

  • Genomics
  • Cancer Biology
  • Molecular Biology

Background:

  • Telomeres protect chromosome ends but crisis arises when they become critically short.
  • Telomere dysfunction is a hallmark of cancer, contributing to genomic instability.
  • Replication stress at short telomeres can lead to DNA breaks and aberrant structures.

Purpose of the Study:

  • To elucidate the mechanisms by which telomere crisis contributes to cancer genome evolution.
  • To investigate the role of replication defects at short telomeres in generating mutagenic repair intermediates.
  • To understand how these repair processes shape the cancer genome.

Main Methods:

  • Analysis of DNA replication intermediates at short telomeres.
  • Investigating the resolution pathways of aberrant replication forks.
  • Characterizing the types of chromosomal rearrangements resulting from telomere crisis.

Main Results:

  • Short telomeres induce replication defects and aberrant fork structures.
  • Microhomology-mediated end joining (MMEJ) resolves these aberrant forks.
  • MMEJ-mediated repair results in chromosomal fusions and complex rearrangements.

Conclusions:

  • Telomere crisis is a significant driver of cancer genome evolution.
  • Replication defects at short telomeres provide substrates for mutagenic repair pathways like MMEJ.
  • Mutagenic repair of telomere dysfunction generates the genomic complexity observed in cancer.