Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 102, Issue 23, Pages 8222-8227Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0503095102
Keywords
human telomerase reverse transcriptase; histone modification; genomic integrity
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Funding
- NCI NIH HHS [K01 CA094223, K01 CA94223] Funding Source: Medline
- NIA NIH HHS [R01 AG023145, R01AG023145] Funding Source: Medline
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Constitutive expression of telomerase prevents senescence and crisis by maintaining telomere homeostasis. However, recent evidence suggests that telomerase is dynamically regulated in normal cells and also contributes to transformation independently of net telomere elongation. Here, we show that suppression of the telomerase catalytic subunit [human telomerase reverse transcriptase (hTERT)] expression abrogates the cellular response to DNA double strand breaks. Loss of hTERT does not alter short-term telomere integrity but instead affects the overall configuration of chromatin. Cells lacking hTERT exhibit increased radiosensitivity, diminished capacity for DNA repair, and fragmented chromosomes, demonstrating that loss of hTERT impairs the DNA damage response.
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