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

Amra Grudic, Åsne Jul-Larsen, Stuart J. Haring, Marc S. Wold, Per Eystein Lønning, Rolf Bjerkvig, Stig Ove Bøe*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

45 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)7267-7278
Number of pages12
JournalNucleic Acids Research
Volume35
Issue number21
DOIs
Publication statusPublished - Dec 2007
Externally publishedYes

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