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

doi:10.1093/nar/gkm738

Back

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

Journal article

Open access

Peer reviewed

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 and Stig Ove Bøe

Nucleic acids research, Vol.35(21), pp.7267-7278

12/2007

DOI: 10.1093/nar/gkm738

PMCID: PMC2175364

PMID: 17959650

Files and links (1)

url

https://doi.org/10.1093/nar/gkm738View

Published (Version of record) Open Access

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.

Molecular Biology

Details

Title: Subtitle: Replication protein A prevents accumulation of single-stranded telomeric DNA in cells that use alternative lengthening of telomeres
Creators: Amra Grudic - Section of Oncology, Department of Medicine, Haukeland University Hospital
Åsne Jul-Larsen - Section of Oncology, Department of Medicine, Haukeland University Hospital
Stuart J Haring - Section of Oncology, Department of Medicine, Haukeland University Hospital
Marc S Wold - Section of Oncology, Department of Medicine, Haukeland University Hospital
Per Eystein Lønning - Section of Oncology, Department of Medicine, Haukeland University Hospital
Rolf Bjerkvig - Section of Oncology, Department of Medicine, Haukeland University Hospital
Stig Ove Bøe - Section of Oncology, Department of Medicine, Haukeland University Hospital
Resource Type: Journal article
Publication Details: Nucleic acids research, Vol.35(21), pp.7267-7278
DOI: 10.1093/nar/gkm738
PMID: 17959650
PMCID: PMC2175364
NLM abbreviation: Nucleic Acids Res
ISSN: 0305-1048
eISSN: 1362-4962
Publisher: Oxford University Press
Language: English
Date published: 12/2007
Academic Unit: Radiation Oncology; Biochemistry and Molecular Biology
Record Identifier: 9984024543002771

Metrics

14 Record Views

56 Times Cited - Web of Science