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  HTERT associates with human telomeres and enhances genomic stability and DNA repair

Sharma, G. G., Gupta, A., Wang, H., Scherthan, H., Dhar, S., Gandhi, V., et al. (2003). HTERT associates with human telomeres and enhances genomic stability and DNA repair. Oncogene, 22(1), 131-146. doi:10.1038/sj.onc.1206063.

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Genre: Journal Article
Alternative Title : Oncogene

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 Creators:
Sharma, Girdhar G., Author
Gupta, Arun, Author
Wang, Huichen, Author
Scherthan, Harry1, Author           
Dhar, Sonu, Author
Gandhi, Varsha, Author
Iliakis, George, Author
Shay, Jerry W., Author
Young, Charles S. H., Author
Pandita, Tej K., Author
Affiliations:
1Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433549              

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Free keywords: hTERT; telomeres; transcription; DNA repair; ionizing radiation
 Abstract: Ectopic expression of telomerase in telomerase-silent cells is sufficient to overcome senescence and to extend cellular lifespan. We show here that the catalytic subunit of human telomerase (hTERT) crosslinks telomeres. This interaction is blocked by the telomere repeat binding factor 1, but not by a dominant negative form of this protein. It is also abolished by destruction of the RNA component of telomerase as well as by mutations in the hTERT protein. Ectopic expression of hTERT leads to transcriptional alterations of a subset of genes and changes in the interaction of the telomeres with the nuclear matrix. This is associated with reduction of spontaneous chromosome damage in G1 cells, enhancement of the kinetics of DNA repair and an increase in NTP levels. The effect on DNA repair is likely indirect as TERT does not directly affect DNA end rejoining in vitro or meiotic recombination in vivo. The observed effects of hTERT occurred rapidly before any significant lengthening of telomeres was observed. Our findings establish an intimate relationship between hTERT-telomere interactions and alteration in transcription of a subset of genes that may lead to increased genomic stability and enhanced repair of genetic damage. These novel functions of telomerase are distinct from its known effect on telomere length and have potentially important biological consequences.

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Language(s): eng - English
 Dates: 2003-01-09
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: eDoc: 127851
ISI: 000180166900014
DOI: 10.1038/sj.onc.1206063
 Degree: -

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Title: Oncogene
  Alternative Title : Oncogene
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 22 (1) Sequence Number: - Start / End Page: 131 - 146 Identifier: ISSN: 0950-9232