Rag mutations reveal robust alternative end joining.

Corneo, Barbara; Wendland, Rebecca L; Deriano, Ludovic; Cui, Xiaoping; Klein, Isaac A; Wong, Serre-Yu; Arnal, Suzzette; Holub, Abigail J; Weller, Geoffrey R; Pancake, Bette A; Shah, Sundeep; Brandt, Vicky L; Meek, Katheryn; Roth, David B

Corneo, Barbara; Wendland, Rebecca L; Deriano, Ludovic; Cui, Xiaoping; Klein, Isaac A; Wong, Serre-Yu; Arnal, Suzzette; Holub, Abigail J; Weller, Geoffrey R; Pancake, Bette A; Shah, Sundeep; Brandt, Vicky L; Meek, Katheryn; Roth, David B.

Afiliación

Corneo B; The Kimmel Center for Biology and Medicine of the Skirball Institute and Department of Pathology, New York University School of Medicine, New York, New York 10016, USA.

Nature ; 449(7161): 483-6, 2007 Sep 27.

Article en En | MEDLINE | ID: mdl-17898768

RESUMEN

Mammalian cells repair DNA double-strand breaks (DSBs) through either homologous recombination or non-homologous end joining (NHEJ). V(D)J recombination, a cut-and-paste mechanism for generating diversity in antigen receptors, relies on NHEJ for repairing DSBs introduced by the Rag1-Rag2 protein complex. Animals lacking any of the seven known NHEJ factors are therefore immunodeficient. Nevertheless, DSB repair is not eliminated entirely in these animals: evidence of a third mechanism, 'alternative NHEJ', appears in the form of extremely rare V(D)J junctions and a higher rate of chromosomal translocations. The paucity of these V(D)J events has suggested that alternative NHEJ contributes little to a cell's overall repair capacity, being operative only (and inefficiently) when classical NHEJ fails. Here we find that removing certain portions of murine Rag proteins reveals robust alternative NHEJ activity in NHEJ-deficient cells and some alternative joining activity even in wild-type cells. We propose a two-tier model in which the Rag proteins collaborate with NHEJ factors to preserve genomic integrity during V(D)J recombination.

Asunto(s)

Proteínas de Unión al ADN/genética; Proteínas de Unión al ADN/metabolismo; Proteínas de Homeodominio/genética; Proteínas de Homeodominio/metabolismo; Recombinación Genética/genética; Animales; Proteínas de Unión al ADN/química; Proteínas de Unión al ADN/deficiencia; Proteínas de Homeodominio/química; Ratones; Modelos Genéticos; Mutación/genética

Buscar en Google

Añadir a Mi BVS

Imprimir

XML

PubMed Links

Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Recombinación Genética / Proteínas de Homeodominio / Proteínas de Unión al ADN Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Nature Año: 2007 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido

Buscar en Google

Añadir a Mi BVS

Imprimir

XML

PubMed Links