The telomerase reverse transcriptase regulates chromatin state and DNA damage responses.
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.
Masutomi
Kenkichi
K
Department of Medical Oncology and Biostatistical Science, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Possemato
Richard
R
Wong
Judy M Y
JM
Currier
Jennifer L
JL
Tothova
Zuzana
Z
Manola
Judith B
JB
Ganesan
Shridar
S
Lansdorp
Peter M
PM
Collins
Kathleen
K
Hahn
William C
WC
D002460:Cell Line; D002843:Chromatin / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins; D005347:Fibroblasts; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012995:Solubility; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000235:genetics / Q000378:metabolism
D002843:Chromatin; D004268:DNA-Binding Proteins; D019098:Telomerase