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Updated: Aug 8, 2026
12:08
Telomere Length and Telomerase Activity; A Yin and Yang of Cell Senescence
Published on: May 22, 2013
Functional interaction between DNA-PKcs and telomerase in telomere length maintenance
Silvia Espejel1, Sonia Franco, Antonella Sgura
1Department of Immunology and Oncology, National Centre of Biotechnology, E-28049 Madrid, Spain.
The EMBO Journal
|November 12, 2002
Summary
DNA-PKcs plays a key role in maintaining telomere length and preventing chromosome fusions. Its absence accelerates telomere shortening and cell cycle arrest in telomerase-deficient cells, impacting aging and cancer.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- DNA-PKcs is crucial for DNA repair via non-homologous end-joining and telomere capping.
- DNA-PKcs deficiency causes telomere-associated chromosome fusions.
- Telomeres shorten with each cell division and are maintained by telomerase.
Purpose of the Study:
- To investigate the role of DNA-PKcs in telomere length maintenance.
- To explore the functional interaction between DNA-PKcs and telomerase.
- To determine DNA-PKcs's role in apoptosis and chromosome fusions triggered by short telomeres.
Main Methods:
- Generation of mice doubly deficient in DNA-PKcs and telomerase (Terc(-/-)/DNA-PKcs(-/-)).
- Comparative analysis of telomere shortening rates in Terc(-/-) and Terc(-/-)/DNA-PKcs(-/-) mice.
- Assessment of end-to-end fusions and apoptosis in response to critically short telomeres.
Main Results:
- Terc(-/-)/DNA-PKcs(-/-) mice exhibited accelerated telomere shortening compared to Terc(-/-) controls.
- DNA-PKcs is essential for end-to-end chromosome fusions and apoptosis induced by critically short telomeres.
- In telomerase-deficient cells, DNA-PKcs absence leads to faster telomere degradation and cell cycle arrest without increased apoptosis or fusion.
Conclusions:
- DNA-PKcs has a fundamental role in telomere length maintenance, interacting functionally with telomerase.
- DNA-PKcs is critical for preventing chromosome fusions and apoptosis when telomeres become critically short.
- DNA-PKcs deficiency may accelerate aging and influence cancer development by impacting telomere dynamics in human somatic cells.
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