Enhanced intra-switch region recombination during immunoglobulin class switch recombination in 53BP1-/- B cells. - Archive ouverte HAL Access content directly
Journal Articles European Journal of Immunology Year : 2007

Enhanced intra-switch region recombination during immunoglobulin class switch recombination in 53BP1-/- B cells.

Junjie Chen
  • Function : Author
André Nussenzweig
  • Function : Author
Michel C Nussenzweig
  • Function : Author

Abstract

Immunoglobulin class switch recombination (CSR) is initiated by activation-induced cytidine deaminase (AID), an enzyme that deaminates cytidine residues in single-stranded DNA. U:G mismatches created by AID are processed to produce lesions that recruit and activate DNA damage response proteins including Ataxia-telangiectasia mutated (ATM), histone H2AX, Nijmegen breakage syndrome 1 (Nbs1), and p53 binding protein 1 (53BP1). Among these proteins, absence of 53BP1 produces the most severe impairment of class switching. Here, we demonstrate that AID is targeted normally to switch region DNA and that intra-switch region recombination is enhanced in 53BP1-/- B cells. In addition, Smicro-Sgamma1 switch region junctions cloned from 53BP1-/- B cells show unusual insertions suggestive of failed class switching. Our data are consistent with a role for 53BP1 in stabilizing the synapsis of switch regions during CSR.
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Dates and versions

hal-00166263 , version 1 (02-08-2007)

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Bernardo Reina-San-Martin, Junjie Chen, André Nussenzweig, Michel C Nussenzweig. Enhanced intra-switch region recombination during immunoglobulin class switch recombination in 53BP1-/- B cells.. European Journal of Immunology, 2007, 37 (1), pp.235-9. ⟨10.1002/eji.200636789⟩. ⟨hal-00166263⟩
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