FANCD2 binds MCM proteins and controls replisome function upon activation of s phase checkpoint signaling.
Mol Cell
; 51(5): 678-90, 2013 Sep 12.
Article
en En
| MEDLINE
| ID: mdl-23993743
ABSTRACT
Proteins disabled in Fanconi anemia (FA) are necessary for the maintenance of genome stability during cell proliferation. Upon replication stress signaling by ATR, the FA core complex monoubiquitinates FANCD2 and FANCI in order to activate DNA repair. Here, we identified FANCD2 and FANCI in a proteomic screen of replisome-associated factors bound to nascent DNA in response to replication arrest. We found that FANCD2 can interact directly with minichromosome maintenance (MCM) proteins. ATR signaling promoted the transient association of endogenous FANCD2 with the MCM2-MCM7 replicative helicase independently of FANCD2 monoubiquitination. FANCD2 was necessary for human primary cells to restrain DNA synthesis in the presence of a reduced pool of nucleotides and prevented the accumulation of single-stranded DNA, the induction of p21, and the entry of cells into senescence. These data reveal that FANCD2 is an effector of ATR signaling implicated in a general replisome surveillance mechanism that is necessary for sustaining cell proliferation and attenuating carcinogenesis.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Proteína del Grupo de Complementación D2 de la Anemia de Fanconi
/
Puntos de Control de la Fase S del Ciclo Celular
/
Componente 2 del Complejo de Mantenimiento de Minicromosoma
/
Componente 7 del Complejo de Mantenimiento de Minicromosoma
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Mol Cell
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2013
Tipo del documento:
Article
País de afiliación:
Francia