Massive telomere loss is an early event of DNA damage-induced apoptosis.
Chromosomal stability and cell viability require a proficient telomeric end-capping function. In particular, telomere dysfunction because of either critical telomere shortening or because of mutation of telomere-binding proteins results in increased apoptosis and/or cell arrest. Here, we show that, in turn, DNA damage-induced apoptosis results in a dramatic telomere loss. In particular, using flow cytometry for simultaneous detection of telomere length and apoptosis, we show that cells undergoing apoptosis upon DNA damage also exhibit a rapid and dramatic loss of telomeric sequences. This telomere loss occurs at early stages of apoptosis, because it does not require caspase-3 activation, and it is induced by loss of the mitochondrial membrane potential (Deltapsi(m)) and production of reactive oxygen species. These observations suggest a direct effect of mitochondrial dysfunction on telomeres.
Ramírez
Rafael
R
Unidad de Investigación, Hospital Universitario Reina Sofia, 14004 Córdoba, Spain. rramirez@hrs.sas.junta-andalucia.es
Carracedo
Julia
J
Jiménez
Rosario
R
Canela
Andres
A
Herrera
Eloísa
E
Aljama
Pedro
P
Blasco
María A
MA
D017209:Apoptosis; D002166:Camptothecin / Q000494:pharmacology; D053148:Caspase 3; D020169:Caspases / Q000502:physiology; D004249:DNA Damage; D004789:Enzyme Activation; D006801:Humans; D011065:Poly(ADP-ribose) Polymerases / Q000502:physiology; D017382:Reactive Oxygen Species; D019098:Telomerase / Q000378:metabolism; D016615:Telomere; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D011065:Poly(ADP-ribose) Polymerases; D019098:Telomerase; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D002166:Camptothecin