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

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.

• Authors: Bernardo Reina-San-Martin, Junjie Chen, André Nussenzweig, Michel C Nussenzweig
• Journal: European journal of immunology (Eur J Immunol) Vol. 37 Issue 1 Pg. 235-9 (Jan 2007) ISSN: 0014-2980 [Print] Germany
• PMID: 17183606 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Immunoglobulin Isotypes
• Intracellular Signaling Peptides and Proteins
• Phosphoproteins
• TP53BP1 protein, human
• Tumor Suppressor p53-Binding Protein 1

Topics

• Animals
• B-Lymphocyte Subsets (immunology, metabolism)
• Base Sequence
• Cell Line, Tumor
• Cells, Cultured
• DNA Damage
• Immunoglobulin Isotypes (biosynthesis)
• Immunoglobulin Switch Region (genetics)
• Intracellular Signaling Peptides and Proteins (deficiency, genetics, physiology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Molecular Sequence Data
• Phosphoproteins (deficiency, genetics, physiology)
• Recombination, Genetic (immunology)
• Somatic Hypermutation, Immunoglobulin (genetics)
• Tumor Suppressor p53-Binding Protein 1