Human Ku70/80 interacts directly with hTR, the RNA component of human telomerase

Maintenance of telomere integrity requires the dynamic interplay between telomerase, telomere-associated proteins and DNA repair proteins. These interactions are vital to suppress DNA damage responses and changes in chromosome dynamics that can result in aneuploidy or other transforming aberrations....

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Bibliographic Details
Published in:Nucleic acids research 2005-01, Vol.33 (7), p.2090-2098
Main Authors: Ting, Nicholas S. Y., Yu, Yaping, Pohorelic, Brant, Lees-Miller, Susan P., Beattie, Tara L.
Format: Article
Language:English
Subjects:
Antigens, Nuclear - metabolism
Binding Sites
Cell Line
DNA Helicases - metabolism
DNA-Binding Proteins - metabolism
Humans
Immunoprecipitation
Ku Autoantigen
RNA
RNA, Long Noncoding
RNA, Untranslated - chemistry
RNA, Untranslated - metabolism
Telomerase - chemistry
Telomerase - metabolism
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Summary:Maintenance of telomere integrity requires the dynamic interplay between telomerase, telomere-associated proteins and DNA repair proteins. These interactions are vital to suppress DNA damage responses and changes in chromosome dynamics that can result in aneuploidy or other transforming aberrations. The interaction between the DNA repair protein Ku and the RNA component of telomerase (TLC1) in Saccharomyces cerevisiae has been shown to be important for maintaining telomere length. Here, we sought to determine whether this interaction was conserved in higher eukaryotes. Although there is no sequence similarity between TLC1 and the RNA component (hTR) of human telomerase, we show that human Ku70/80 interacts with hTR both in vitro and in a cellular context. Specifically, Ku70/80 interacts with a 47 nt region of the 3′ end of hTR, which resembles the stem–loop region of the yeast Ku70/80 binding domain on TLC1. Furthermore, utilizing immunoprecipitation/RT–PCR experiments, we show that Ku interacts with hTR in cell lines deficient in the human telomerase reverse transcriptase protein (hTERT), suggesting that this interaction does not require hTERT. These data suggest that Ku interacts directly with hTR, independent of hTERT, providing evidence for the conservation of the interaction between Ku and telomerase RNA among various species and provide significant insight into how Ku is involved in telomere maintenance in higher eukaryotes.
ISSN:0305-1048
1362-4962
1362-4962
DOI:10.1093/nar/gki342