Document Detail


The Bloom syndrome helicase BLM interacts with TRF2 in ALT cells and promotes telomeric DNA synthesis.
MedLine Citation:
PMID:  12444098     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Telomerase-negative immortalized human cells maintain telomeres by alternative lengthening of telomeres (ALT) pathway(s), which may involve homologous recombination. We find that endogenous BLM protein co-localizes with telomeric foci in ALT human cells but not telomerase positive immortal cell lines or primary cells. BLM interacts in vivo with the telomeric protein TRF2 in ALT cells, as detected by FRET and co-immunoprecipitation. Transient over-expression of green fluorescent protein (GFP)-BLM results in marked, ALT cell-specific increases in telomeric DNA. The association of BLM with telomeres and its effect on telomere DNA synthesis require a functional helicase domain. Our results identify BLM as the first protein found to affect telomeric DNA synthesis exclusively in human ALT cells and suggest that BLM facilitates recombination-driven amplification of telomeres in ALT cells.
Authors:
Dimitrios J Stavropoulos; Paul S Bradshaw; Xiaobin Li; Ivan Pasic; Kevin Truong; Mitsuhiko Ikura; Mark Ungrin; M Stephen Meyn
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Human molecular genetics     Volume:  11     ISSN:  0964-6906     ISO Abbreviation:  Hum. Mol. Genet.     Publication Date:  2002 Dec 
Date Detail:
Created Date:  2002-11-21     Completed Date:  2003-05-19     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9208958     Medline TA:  Hum Mol Genet     Country:  England    
Other Details:
Languages:  eng     Pagination:  3135-44     Citation Subset:  IM    
Affiliation:
Department of Molecular and Medical Genetics, University of Toronto, Toronto, Canada M5S 1A8.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphatases / biosynthesis,  immunology,  metabolism*
Bloom Syndrome / enzymology*,  genetics*
Cell Line
Cell Line, Transformed
Cell Nucleus
DNA / biosynthesis*
DNA Helicases / biosynthesis,  immunology,  metabolism*
Fibroblasts / chemistry,  enzymology,  virology
Green Fluorescent Proteins
Humans
Luminescent Proteins / biosynthesis,  genetics
RecQ Helicases
Recombinant Proteins / biosynthesis,  genetics
Telomere / enzymology,  genetics,  metabolism*
Telomeric Repeat Binding Protein 2 / immunology,  metabolism*
Chemical
Reg. No./Substance:
0/Luminescent Proteins; 0/Recombinant Proteins; 0/Telomeric Repeat Binding Protein 2; 147336-22-9/Green Fluorescent Proteins; 9007-49-2/DNA; 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

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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