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MutSalpha binds to and promotes synapsis of transcriptionally activated immunoglobulin switch regions.
- Source :
-
Current biology : CB [Curr Biol] 2005 Mar 08; Vol. 15 (5), pp. 470-4. - Publication Year :
- 2005
-
Abstract
- Immunoglobulin class switch recombination joins a new constant (C) region to the rearranged and expressed heavy chain variable (VDJ) region in antigen-activated B cells (Figure 1A) (reviewed in [1, 2]). Switch recombination is activated by transcription of intronic, G-rich and repetitive switch (S) regions and produces junctions that are heterogeneous in sequence and position in the S regions. Switch recombination depends upon the B cell-specific cytidine deaminase, AID, and conserved DNA repair factors, including the mismatch repair heterodimer, MutSalpha (MSH2/MSH6). In mice, ablation of Msh2 or Msh6, but not Msh3, decreases levels of switch recombination and diminishes heterogeneity of switch junctions [3-7]. Here, we demonstrate that MSH2 associates with transcribed S regions in primary murine B cells activated for switch recombination. Electron microscopic imaging reveals that MutSalpha binds in vitro to DNA structures formed within transcribed S regions and mediates their synapsis. MutSalpha binds with high affinity to G4 DNA formed upon transcription of the S regions and also binds to U.G mismatches, initial products of DNA deamination by AID. These results suggest that MutSalpha interacts with the S regions in switching B cells to promote DNA synapsis and recombination.
- Subjects :
- Animals
B-Lymphocytes ultrastructure
Base Pair Mismatch
Chromatin metabolism
Cytosine Deaminase metabolism
DNA Primers
DNA Repair Enzymes metabolism
DNA Repair Enzymes physiology
DNA-Binding Proteins isolation & purification
DNA-Binding Proteins physiology
Electrophoresis, Polyacrylamide Gel
Electrophoretic Mobility Shift Assay
Immunoprecipitation
Mice
Microscopy, Electron
MutS Homolog 2 Protein
Oligonucleotides
Proto-Oncogene Proteins isolation & purification
Proto-Oncogene Proteins physiology
B-Lymphocytes metabolism
Chromosome Pairing physiology
DNA-Binding Proteins metabolism
Immunoglobulin Class Switching physiology
Immunoglobulin Switch Region physiology
Proto-Oncogene Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0960-9822
- Volume :
- 15
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Current biology : CB
- Publication Type :
- Academic Journal
- Accession number :
- 15753043
- Full Text :
- https://doi.org/10.1016/j.cub.2004.12.077