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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.
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
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...
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...

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Related Experiment Video

Updated: Jun 6, 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

Complex structural variations functionally inactivate the telomerase chaperone TCAB1 in osteosarcoma.

Joshua Keegan1, Sydney Sorbello1,2, Joakin Mori3

  • 1Department of Pharmacology, Physiology & Biophysics, Boston, MA, 02118, USA.

BMC Cancer
|June 4, 2026
PubMed
Summary
This summary is machine-generated.

Pediatric osteosarcoma often activates the alternative lengthening of telomeres (ALT) pathway. Researchers found structural variants in TP53 that also inactivate TCAB1, a key telomerase component, contributing to ALT activation.

Keywords:
Alternative lengthening of telomeresGenomic instabilityOsteosarcomaStructural variantsTP53TelomeraseWRAP53/TCAB1

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Last Updated: Jun 6, 2026

Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer
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Published on: July 14, 2011

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The alternative lengthening of telomeres (ALT) pathway drives cellular immortalization in 75% of pediatric osteosarcomas.
  • While ALT mechanisms are being elucidated, the genetic mutations activating it remain largely unknown.
  • TP53 gene mutations are common in osteosarcoma, often involving structural variants (SVs) in its first intron.

Purpose of the Study:

  • To investigate the spectrum of genetic mutations underlying ALT pathway activation in osteosarcoma.
  • To identify novel genetic events contributing to the development of pediatric osteosarcoma.
  • To explore the relationship between TP53 structural variants and the inactivation of neighboring genes.

Main Methods:

  • Whole-genome sequencing of pediatric osteosarcoma samples.
  • Analysis of structural variants (SVs) within the TP53 gene and its vicinity.
  • Correlation of identified SVs with ALT pathway activation status.

Main Results:

  • Structural variants (SVs) within the TP53 gene were identified in osteosarcoma tumors.
  • These TP53 SVs were found to also inactivate the TCAB1 gene (also known as WRAP53).
  • TCAB1 inactivation via SVs was prevalent in approximately 40% of ALT-positive osteosarcoma tumors.

Conclusions:

  • Functional inactivation of the telomerase holoenzyme component TCAB1 is a previously unrecognized event in ALT-positive osteosarcoma.
  • TP53 structural variants that compromise TP53 also contribute to TCAB1 inactivation, promoting ALT pathway activation.
  • These findings highlight a novel mechanism contributing to cellular immortalization in pediatric osteosarcoma.