Nuclear-receptor-mediated telomere insertion leads to genome instability in ALT cancers.
Cell
; 160(5): 913-927, 2015 Feb 26.
Article
en En
| MEDLINE
| ID: mdl-25723166
ABSTRACT
The breakage-fusion-bridge cycle is a classical mechanism of telomere-driven genome instability in which dysfunctional telomeres are fused to other chromosomal extremities, creating dicentric chromosomes that eventually break at mitosis. Here, we uncover a distinct pathway of telomere-driven genome instability, specifically occurring in cells that maintain telomeres with the alternative lengthening of telomeres mechanism. We show that, in these cells, telomeric DNA is added to multiple discrete sites throughout the genome, corresponding to regions regulated by NR2C/F transcription factors. These proteins drive local telomere DNA addition by recruiting telomeric chromatin. This mechanism, which we name targeted telomere insertion (TTI), generates potential common fragile sites that destabilize the genome. We propose that TTI driven by NR2C/F proteins contributes to the formation of complex karyotypes in ALT tumors.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Telómero
/
Receptores de N-Metil-D-Aspartato
/
Inestabilidad Genómica
/
Neoplasias
Límite:
Humans
Idioma:
En
Revista:
Cell
Año:
2015
Tipo del documento:
Article
País de afiliación:
Francia