Replication protein A prevents accumulation of single-stranded telomeric DNA in cells that use alternative lengthening of telomeres

Nucleic Acids Res. 2007;35(21):7267-78. doi: 10.1093/nar/gkm738. Epub 2007 Oct 24.


The activation of a telomere maintenance mechanism is required for cancer development in humans. While most tumors achieve this by expressing the enzyme telomerase, a fraction (5-15%) employs a recombination-based mechanism termed alternative lengthening of telomeres (ALT). Here we show that loss of the single-stranded DNA-binding protein replication protein A (RPA) in human ALT cells, but not in telomerase-positive cells, causes increased exposure of single-stranded G-rich telomeric DNA, cell cycle arrest in G2/M phase, accumulation of single-stranded telomeric DNA within ALT-associated PML bodies (APBs), and formation of telomeric aggregates at the ends of metaphase chromosomes. This study demonstrates differences between ALT cells and telomerase-positive cells in the requirement for RPA in telomere processing and implicates the ALT mechanism in tumor cells as a possible therapeutic target.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle
  • Cell Line, Transformed
  • Cell Line, Tumor
  • DNA, Single-Stranded / metabolism*
  • Humans
  • Neoplasms / genetics*
  • RNA Interference
  • Replication Protein A / antagonists & inhibitors
  • Replication Protein A / physiology*
  • Telomere / chemistry
  • Telomere / metabolism*


  • DNA, Single-Stranded
  • Replication Protein A