| Topoisomerase IIIalpha is required for normal proliferation and telomere stability in alternative lengthening of telomeres. | |
| | |
MedLine Citation:
|
PMID: 18418389 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Topoisomerase (Topo) IIIalpha associates with BLM helicase, which is proposed to be important in the alternative lengthening of telomeres (ALT) pathway that allows telomere recombination in the absence of telomerase. Here, we show that human Topo IIIalpha colocalizes with telomeric proteins at ALT-associated promyelocytic bodies from ALT cells. In these cells, Topo IIIalpha immunoprecipitated with telomere binding protein (TRF) 2 and BLM and was shown to be associated with telomeric DNA by chromatin immunoprecipitation, suggesting that these proteins form a complex at telomere sequences. Topo IIIalpha depletion by small interfering RNA reduced ALT cell survival, but did not affect telomerase-positive cell lines. Moreover, repression of Topo IIIalpha expression in ALT cells reduced the levels of TRF2 and BLM proteins, provoked a strong increase in the formation of anaphase bridges, induced the degradation of the G-overhang signal, and resulted in the appearance of DNA damage at telomeres. In contrast, telomere maintenance and TRF2 levels were unaffected in telomerase-positive cells. We conclude that Topo IIIalpha is an important telomere-associated factor, essential for telomere maintenance and chromosome stability in ALT cells, and speculate on its potential mechanistic function. |
| | |
Authors:
|
Nassima Temime-Smaali; Lionel Guittat; Thomas Wenner; Emilie Bayart; Céline Douarre; Dennis Gomez; Marie-Josèphe Giraud-Panis; Arturo Londono-Vallejo; Eric Gilson; Mounira Amor-Guéret; Jean-François Riou |
Related Documents
:
|
15093749 - Histone deacetylase inhibitors induce a senescence-like state in human cells by a p16-d... 14718559 - The transcriptome of prematurely aging yeast cells is similar to that of telomerase-def... 20569479 - Senescent mouse cells fail to overtly regulate the hira histone chaperone and do not fo... 20518889 - Detection of telomerase activity in cultured cells and tumor tissue of lung carcinoma b... 12475949 - Peroxisome senescence in human fibroblasts. 374899 - Cellular replication and aging. 1620729 - Quenching of singlet oxygen by biomolecules from l1210 leukemia cells. 6328229 - Transformation of human embryonic kidney cells by a viable deletion mutant of bk virus. 3948489 - Hypogonadal states in the male. |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-04-17 |
Journal Detail:
|
Title: The EMBO journal Volume: 27 ISSN: 1460-2075 ISO Abbreviation: EMBO J. Publication Date: 2008 May |
Date Detail:
|
Created Date: 2008-05-22 Completed Date: 2008-06-16 Revised Date: 2009-11-19 |
Medline Journal Info:
|
Nlm Unique ID: 8208664 Medline TA: EMBO J Country: England |
Other Details:
|
Languages: eng Pagination: 1513-24 Citation Subset: IM |
Affiliation:
|
Laboratoire d'Onco-Pharmacologie, JE 2428, UFR de Pharmacie, Université de Reims Champagne-Ardenne, Reims, France. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adenosine Triphosphatases
/
analysis,
metabolism Anaphase Cell Line Cell Proliferation / drug effects Chromatin Immunoprecipitation Chromosomal Instability* / genetics DNA Helicases / analysis, metabolism DNA Topoisomerases, Type I / analysis, genetics, metabolism* Humans Neoplasm Proteins / analysis, metabolism Nuclear Proteins / analysis, metabolism Protein Subunits / analysis, metabolism RNA, Small Interfering / genetics, pharmacology RecQ Helicases Telomere / metabolism*, ultrastructure* Telomere-Binding Proteins / analysis, metabolism Telomeric Repeat Binding Protein 2 / analysis, metabolism Transcription Factors / analysis, metabolism Tumor Suppressor Proteins / analysis, metabolism |
| Chemical | |
Reg. No./Substance:
|
0/Neoplasm Proteins; 0/Nuclear Proteins; 0/Protein Subunits; 0/RNA, Small Interfering; 0/TERF2 protein, human; 0/Telomere-Binding Proteins; 0/Telomeric Repeat Binding Protein 2; 0/Transcription Factors; 0/Tumor Suppressor Proteins; 0/shelterin, human; 143220-95-5/PML protein, human; EC 3.6.1.-/Adenosine Triphosphatases; EC 3.6.1.-/Bloom syndrome protein; EC 3.6.1.-/DNA Helicases; EC 3.6.1.-/RecQ Helicases; EC 5.99.1.2/DNA Topoisomerases, Type I; EC 5.99.1.2/topoisomerase IIIalpha |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Yeast and human Ysl2p/hMon2 interact with Gga adaptors and mediate their subcellular distribution.
Next Document: Characteristics and expectations of patients with erectile dysfunction: results of the SCORED study.