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Telomere loss provokes multiple pathways to apoptosis and produces genomic instability in Drosophila melanogaster

Simon W A Titen1, Kent G Golic

  • 1Department of Biology, University of Utah, Salt Lake City, Utah 84112, USA.

Genetics
|October 11, 2008
PubMed

Insights

Loss of a single telomere in Drosophila can trigger cell death through multiple pathways. However, some cells survive, exhibiting genomic instability and aneuploidy characteristic of early cancer.

Area of Science:

  • Cell Biology
  • Genetics
  • Developmental Biology

Background:

  • Telomeres protect chromosome ends from degradation and fusion.
  • Telomere loss can lead to genomic instability and cell death.
  • Apoptotic pathways, including p53-dependent and independent routes, act as safeguards against damaged cells.

Purpose of the Study:

  • To investigate the consequences of telomere loss in Drosophila melanogaster development.
  • To elucidate the cellular mechanisms and pathways involved in response to telomere loss.
  • To determine if telomere loss can induce phenotypes resembling early-stage cancer cells.

Main Methods:

  • Induced dicentric chromosome breakage to generate telomere loss in Drosophila.
  • Analysis of apoptotic pathways (p53-dependent and independent) triggered by telomere loss.
  • Observation of cellular and genomic abnormalities in surviving cells, including aneuploidy and chromosome fusions.

Main Results:

  • Telomere loss induced significant cell death via p53-dependent (Chk1/Chk2) and p53-independent apoptotic pathways.
  • A fraction of cells escaped apoptosis, accumulating karyotypic abnormalities like end-to-end fusions, anaphase bridges, aneuploidy, and polyploidy.
  • Genomic instability, including bridge-breakage-fusion cycles and persistence of acentric chromosome segments, was exacerbated when apoptotic mechanisms were impaired.
  • Loss of a single telomere was sufficient to generate phenotypes of early cancer cells, characterized by multi-chromosomal genomic instability and aneuploidy.

Conclusions:

  • Telomere loss is a potent trigger for both cell death and genomic instability in Drosophila.
  • Evasion of apoptosis following telomere loss leads to cancer-like genomic abnormalities.
  • Aneuploidy arising from telomere loss may contribute to the sustained escape of cells from checkpoint controls, promoting cancer development.

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