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Functional interaction between DNA-PKcs and telomerase in telomere length maintenance.
- Source :
-
EMBO Journal . 11/15/2002, Vol. 21 Issue 22, p6275-6287. 13p. - Publication Year :
- 2002
-
Abstract
- DNA-PKcs is the catalytic subunit of the DNA- dependent protein kinase (DNA-PK) complex that functions in the non-homologous end-joining of double-strand breaks, and it has been shown previously to have a role in telomere capping. In particular, DNA-PKcs deficiency leads to chromosome fusions involving telomeres produced by leading-strand synthesis. Here, by generating mice doubly deficient in DNA-PKcs and telomerase (Terc-/-/DNA-PKcs-/-), we demonstrate that DNA-PKcs also has a fundamental role in telomere length maintenance. In particular, Terc-/-/DNA-PKcs-/- mice displayed an accelerated rate of telomere shortening when compared with Terc-/- controls, suggesting a functional interaction between both activities in maintaining telomere length. In addition, we also provide direct demonstration that DNA-PKcs is essential for both end-to-end fusions and apoptosis triggered by critically short telomeres. Our data predict that, in telomerase-deficient cells, i.e. human somatic cells, DNA-PKcs abrogation may lead to a faster rate of telomere degradation and cell cycle arrest in the absence of increased apoptosis and/or fusion of telomere-exhausted chromosomes. These results suggest a critical role of DNA-PKcs in both cancer and aging. [ABSTRACT FROM AUTHOR]
- Subjects :
- *DNA
*GENES
*TELOMERES
*CHROMOSOMES
*DEOXYRIBOSE
*CANCER
Subjects
Details
- Language :
- English
- ISSN :
- 02614189
- Volume :
- 21
- Issue :
- 22
- Database :
- Academic Search Index
- Journal :
- EMBO Journal
- Publication Type :
- Academic Journal
- Accession number :
- 12956236
- Full Text :
- https://doi.org/10.1093/emboj/cdf593