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

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.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Grudic A,Jul-Larsen A,Haring SJ,Wold MS,Lønning PE,Bjerkvig R,Bøe SO

doi

10.1093/nar/gkm738

subject

Has Abstract

pub_date

2007-01-01 00:00:00

pages

7267-78

issue

21

eissn

0305-1048

issn

1362-4962

pii

gkm738

journal_volume

35

pub_type

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