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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

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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 DNA.
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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 the telomeric...
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MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA ends...
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Inhibition of telomerase activity correlates with a decrease in the RNA component of telomerase during

T Kobayashi1, K Clodi, Y Yang

  • 1UNIV TEXAS,MD ANDERSON CANC CTR,DEPT NEUROONCOL & TUMOR BIOL,HOUSTON,TX 77030. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT HEMATOL,HOUSTON,TX 77030. MIE UNIV,SCH MED,DEPT INTERNAL MED 2,TSU,MIE 514,JAPAN. UNIV TEXAS,SW MED CTR,DEPT CELL BIOL & NEUROSCI,DALLAS,TX 75235.

International Journal of Oncology
|April 30, 2011
PubMed
Summary

Differentiation of leukemia cells inhibits telomerase activity, not by a diffusible inhibitor, but through decreased telomerase RNA and increased G(0) phase cells. This impacts cancer research and telomere biology.

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Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Normal somatic cells experience telomere shortening due to limited telomerase activity.
  • Telomerase, a ribonucleoprotein, maintains telomere length and is reactivated in tumor cells.
  • Previous studies indicated differentiation agents inhibit telomerase in HL60 leukemia cells.

Purpose of the Study:

  • To investigate the mechanism of telomerase inhibition during HL60 leukemia cell differentiation.
  • To determine if a diffusible inhibitor is responsible for decreased telomerase activity.
  • To correlate telomerase activity changes with cellular markers and RNA expression.

Main Methods:

  • Treatment of HL60 leukemia cells with differentiation-inducing agents.
  • Analysis of telomerase activity.
  • Measurement of CD11b surface marker expression.
  • Protein extract mixing experiments.
  • Assessment of total cellular RNA and telomerase RNA levels.
  • Cell cycle analysis (G(0) phase).

Main Results:

  • Decreased telomerase activity did not correlate with CD11b expression timing.
  • No diffusible telomerase inhibitor was detected in differentiated cells.
  • Reduced telomerase activity correlated with decreased telomerase RNA expression.
  • A decrease in total cellular RNA levels was observed.
  • An increase in cells at the G(0) phase was noted.

Conclusions:

  • Telomerase inhibition in differentiating HL60 cells is not mediated by a diffusible inhibitor.
  • The decrease in telomerase activity is linked to reduced telomerase RNA expression and an accumulation of cells in the G(0) phase.
  • These findings provide insight into the regulation of telomerase during cellular differentiation and its implications for cancer biology.