Pot1a prevents telomere dysfunction and ATM-dependent neuronal loss.
J Neurosci
; 34(23): 7836-44, 2014 Jun 04.
Article
en En
| MEDLINE
| ID: mdl-24899707
ABSTRACT
Genome stability is essential for neural development and the prevention of neurological disease. Here we determined how DNA damage signaling from dysfunctional telomeres affects neurogenesis. We found that telomere uncapping by Pot1a inactivation resulted in an Atm-dependent loss of cerebellar interneurons and granule neuron precursors in the mouse nervous system. The activation of Atm by Pot1a loss occurred in an Atr-dependent manner, revealing an Atr to Atm signaling axis in the nervous system after telomere dysfunction. In contrast to telomere lesions, Brca2 inactivation in neural progenitors also led to ablation of cerebellar interneurons, but this did not require Atm. These data reveal that neural cell loss after DNA damage selectively engages Atm signaling, highlighting how specific DNA lesions can dictate neuropathology arising in human neurodegenerative syndromes.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Daño del ADN
/
Telómero
/
Proteínas de Unión al ADN
/
Neuronas
Límite:
Animals
Idioma:
En
Revista:
J Neurosci
Año:
2014
Tipo del documento:
Article