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

被引：56

作者：

Grudic, Amra ^{[1
,2
]}

Jul-Larsen, Asne ^{[1
,2
]}

Haring, Stuart J. ^{[3
]}

Wold, Marc S. ^{[3
]}

Lonning, Per Eystein ^{[2
]}

Bjerkvig, Rolf ^{[2
,4
]}

Boe, Stig Ove ^{[1
,2
]}

机构：

[1] Univ Bergen, Dept Biomed, Sect Anat Cell Biol, N-5009 Bergen, Norway

[2] Haukeland Hosp, Dept Med, Sect Oncol, Bergen, Norway

[3] Univ Iowa Carver Coll Med, Dept Biochem, Iowa City, IA 52242 USA

[4] NorLux, Ctr Rec Publ Sante, Luxembourg, Luxembourg

来源：

NUCLEIC ACIDS RESEARCH | 2007年 / 35卷 / 21期

关键词：

D O I：

10.1093/nar/gkm738

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

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.

引用

页码：7267 / 7278

页数：12

共 42 条

[1]

Loss of RPA1 induces Chk2 phosphorylation through a caffeine-sensitive pathway [J].