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Nucleic Acids Res. 2007;35(21):7267-78. Epub 2007 Oct 24.

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

Author information

1
Section of Oncology, Department of Medicine, Haukeland University Hospital.

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.

PMID:
17959650
PMCID:
PMC2175364
DOI:
10.1093/nar/gkm738
[Indexed for MEDLINE]
Free PMC Article

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