Opposite effects of GCN5 and PCAF knockdowns on the alternative mechanism of telomere maintenance

Oncotarget. 2017 Apr 18;8(16):26269-26280. doi: 10.18632/oncotarget.15447.

Abstract

Cancer cells can use a telomerase-independent mechanism, known as alternative lengthening of telomeres (ALT), to elongate their telomeres. General control non-derepressible 5 (GCN5) and P300/CBP-associated factor (PCAF) are two homologous acetyltransferases that are mutually exclusive subunits in SAGA-like complexes. Here, we reveal that down regulation of GCN5 and PCAF had differential effects on some phenotypic characteristics of ALT cells. Our results suggest that GCN5 is present at telomeres and opposes telomere recombination, in contrast to PCAF that may indirectly favour them in ALT cells.

Keywords: ALT; GCN5; PCAF; telomere recombination.

MeSH terms

  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Proliferation
  • Gene Expression
  • Gene Knockdown Techniques
  • Genetic Association Studies*
  • Genomic Instability
  • Humans
  • Intranuclear Inclusion Bodies / genetics
  • Intranuclear Inclusion Bodies / metabolism
  • Leukemia, Promyelocytic, Acute / genetics
  • Leukemia, Promyelocytic, Acute / metabolism
  • Leukemia, Promyelocytic, Acute / pathology
  • Protein Binding
  • Sister Chromatid Exchange
  • Telomere / genetics*
  • Telomere Homeostasis / genetics*
  • Translocation, Genetic
  • p300-CBP Transcription Factors / genetics*

Substances

  • p300-CBP Transcription Factors
  • p300-CBP-associated factor