GANP regulates the choice of DNA repair pathway by DNA-PKcs interaction in AID-dependent IgV region diversification.
J Immunol
; 192(12): 5529-39, 2014 Jun 15.
Article
em En
| MEDLINE
| ID: mdl-24808370
ABSTRACT
RNA export factor germinal center-associated nuclear protein (GANP) interacts with activation-induced cytidine deaminase (AID) and shepherds it from the cytoplasm to the nucleus and toward the IgV region loci in B cells. In this study, we demonstrate a role for GANP in the repair of AID-initiated DNA damage in chicken DT40 B cells to generate IgV region diversity by gene conversion and somatic hypermutation. GANP plays a positive role in IgV region diversification of DT40 B cells in a nonhomologous end joining-proficient state. DNA-PKcs physically interacts with GANP, and this interaction is dissociated by dsDNA breaks induced by a topoisomerase II inhibitor, etoposide, or AID overexpression. GANP affects the choice of DNA repair mechanism in B cells toward homologous recombination rather than nonhomologous end joining repair. Thus, GANP presumably plays a critical role in protection of the rearranged IgV loci by favoring homologous recombination of the DNA breaks under accelerated AID recruitment.
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Base de dados:
MEDLINE
Assunto principal:
Fosfoproteínas
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Região Variável de Imunoglobulina
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Proteínas Nucleares
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Citidina Desaminase
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Hipermutação Somática de Imunoglobulina
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Proteínas de Ligação a DNA
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Reparo do DNA
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Proteína Quinase Ativada por DNA
Limite:
Animals
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article