Mutagenesis dependent upon the combination of activation-induced deaminase expression and a double-strand break.
Mol Immunol
; 48(1-3): 164-70, 2010.
Article
em En
| MEDLINE
| ID: mdl-20828826
ABSTRACT
We explored DNA metabolic events potentially relevant to somatic hypermutation (SHM) of immunoglobulin genes using a yeast model system. Double-strand break (DSB) formation has been discussed as a possible component of the SHM process during immunoglobulin gene maturation. Yet, possible mechanisms linking DSB formation with mutagenesis have not been well understood. In the present study, a linkage between mutagenesis in a reporter gene and a double-strand break at a distal site was examined as a function of activation-induced deaminase (AID) expression. Induction of the DSB was found to be associated with mutagenesis in a genomic marker gene located 7 kb upstream of the break site mutagenesis was strongest with the combination of AID expression and DSB induction. The mutation spectrum of this DSB and AID-mediated mutagenesis was characteristic of replicative bypass of uracil in one strand and was dependent on expression of DNA polymerase delta (Polδ). These results in a yeast model system illustrate that the combination of DSB induction and AID expression could be associated with mutagenesis observed in SHM. Implications of these findings for SHM of immunoglobulin genes in human B cells are discussed.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Mutagênese
/
Citidina Desaminase
/
Hipermutação Somática de Imunoglobulina
/
Quebras de DNA de Cadeia Dupla
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article