ATM and CDK2 control chromatin remodeler CSB to inhibit RIF1 in DSB repair pathway choice.
Nat Commun
; 8(1): 1921, 2017 12 04.
Article
en En
| MEDLINE
| ID: mdl-29203878
ABSTRACT
CSB, a member of the SWI2/SNF2 superfamily, is implicated in DNA double-strand break (DSB) repair. However, how it regulates this repair process is poorly understood. Here we uncover that CSB interacts via its newly identified winged helix domain with RIF1, an effector of 53BP1, and that this interaction mediates CSB recruitment to DSBs in S phase. At DSBs, CSB remodels chromatin by evicting histones, which limits RIF1 and its effector MAD2L2 but promotes BRCA1 accumulation. The chromatin remodeling activity of CSB requires not only damage-induced phosphorylation on S10 by ATM but also cell cycle-dependent phosphorylation on S158 by cyclin A-CDK2. Both modifications modulate the interaction of the CSB N-terminal region with its ATPase domain, the activity of which has been previously reported to be autorepressed by the N-terminal region. These results suggest that ATM and CDK2 control the chromatin remodeling activity of CSB in the regulation of DSB repair pathway choice.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
ADN Helicasas
/
Enzimas Reparadoras del ADN
/
Ensamble y Desensamble de Cromatina
/
Reparación del ADN
/
Quinasa 2 Dependiente de la Ciclina
/
Roturas del ADN de Doble Cadena
/
Proteínas de la Ataxia Telangiectasia Mutada
/
Proteínas de Unión a Poli-ADP-Ribosa
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2017
Tipo del documento:
Article
País de afiliación:
Canadá