CtIP promotes microhomology-mediated alternative end joining during class-switch recombination.
Nat Struct Mol Biol
; 18(1): 75-9, 2011 Jan.
Article
en En
| MEDLINE
| ID: mdl-21131982
ABSTRACT
Immunoglobulin heavy chain (Igh locus) class-switch recombination (CSR) requires targeted introduction of DNA double strand breaks (DSBs) into repetitive 'switch'-region DNA elements in the Igh locus and subsequent ligation between distal DSBs. Both canonical nonhomologous end joining (C-NHEJ) that seals DNA ends with little or no homology and a poorly defined alternative end joining (A-NHEJ, also known as alt-NHEJ) process that requires microhomology ends for ligation have been implicated in CSR. Here, we show that the DNA end-processing factor CtIP is required for microhomology-directed A-NHEJ during CSR. Additionally, we demonstrate that microhomology joins that are enriched upon depletion of the C-NHEJ component Ku70 require CtIP. Finally, we show that CtIP binds to switch-region DNA in a fashion dependent on activation-induced cytidine deaminase. Our results establish CtIP as a bona fide component of microhomology-dependent A-NHEJ and unmask a hitherto unrecognized physiological role of microhomology-mediated end joining in a C-NHEJ-proficient environment.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Recombinación Genética
/
Proteínas Portadoras
/
Cambio de Clase de Inmunoglobulina
/
Proteínas de Ciclo Celular
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Nat Struct Mol Biol
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2011
Tipo del documento:
Article
País de afiliación:
Estados Unidos