Document Detail


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
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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:  2013-04-24    
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.
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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/DNA topoisomerase III
Comments/Corrections

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