Benvenuti nell'Anagrafe della Ricerca d'Ateneo
La valutazione delle attività di ricerca che si svolgono nelle università ha assunto un'importanza rilevante sia per l'intero sistema universitario sia all'interno di ogni singolo ateneo. Roma Tre si è quindi dotata di idonei strumenti informativi in grado di supportare al meglio le azioni di monitoraggio e di valutazione delle attività di ricerca svolte nei propri dipartimentied ha realizzato una Anagrafe della Ricerca di Ateneo.
EnglishDNA-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.
| Titolo: | Functional interaction between DNA-PKcs and telomerase in telomere length maintenance. * Espejel, Franco and Sgura contributed equally to this work |
| Autori: | |
| Data di pubblicazione: | 2002 |
| Rivista: | |
| Citazione: | Espejel S, Franco S, Sgura A, Gae D, Bailey SM, Taccioli GE, et al. (2002). Functional interaction between DNA-PKcs and telomerase in telomere length maintenance. * Espejel, Franco and Sgura contributed equally to this work. EMBO JOURNAL, 21, 6275-6287. |
| 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. |
| Handle: | http://hdl.handle.net/11590/118155 |
| Appare nelle tipologie: | 1.1 Articolo in rivista |
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