53BP1 Supports Immunoglobulin Class Switch Recombination Independently of Its DNA Double-Strand Break End Protection Function.
Cell Rep
; 28(6): 1389-1399.e6, 2019 08 06.
Article
em En
| MEDLINE
| ID: mdl-31390554
ABSTRACT
Class switch recombination (CSR) is a DNA recombination reaction that diversifies the effector functions of antibodies. CSR occurs via the formation and non-homologous end joining (NHEJ) repair of programmed DNA double-strand breaks (DSBs) at the immunoglobulin heavy chain locus. The DNA repair factors 53BP1 and Rif1 promote NHEJ and CSR by protecting DSBs against resection. However, to what extent repression of DNA end resection contributes to CSR is unknown. Here, we show that B lymphocytes devoid of 53BP1-Rif1-dependent DSB end protection activity undergo robust CSR. Inactivation of specific sets of phospho-sites within 53BP1 N-terminal SQ/TQ motifs abrogates Rif1 recruitment and inhibition of resection but only mildly reduces CSR. Furthermore, mutations within 53BP1 oligomerization domain abolish CSR without substantially affecting DNA end processing. Thus, inhibition of DNA end resection does not correlate with CSR efficiency, indicating that regulation of DSB processing is not a key determinant step in CSR.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Switching de Imunoglobulina
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Reparo do DNA por Junção de Extremidades
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Proteína 1 de Ligação à Proteína Supressora de Tumor p53
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Cell Rep
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Alemanha