期刊
EMBO JOURNAL
卷 22, 期 21, 页码 5893-5903出版社
OXFORD UNIV PRESS
DOI: 10.1093/emboj/cdg550
关键词
class switch recombination; mismatch repair; Msh2; mutations; TdT
资金
- NIAID NIH HHS [AI42108, R01 AI023283, AI23283] Funding Source: Medline
Nucleotide substitutions are found in recombined Ig switch (S) regions and also in unrecombined (germline, GL) Smu segments in activated splenic B cells. Herein we examine whether mutations are also introduced into the downstream acceptor S regions prior to switch recombination, but find very few mutations in GL Sgamma3 and Sgamma1 regions in activated B cells. These data suggest that switch recombination initiates in the Smu segment and secondarily involves the downstream acceptor S region. Furthermore, the pattern and specificity of mutations in GL and recombined Smu segments differ, suggesting different repair mechanisms. Mutations in recombined Smu regions show a strong bias toward G/C base pairs and WRCY/RGYW hotspots, whereas mutations introduced into the GL Smu do not. Additionally, induction conditions affect mutation specificity within the GL Smu segment. Mutations are most frequent near the S-S junctions and decrease rapidly with distance from the junction. Finally, we find that mice expressing a transgene for terminal deoxynucleotidyl transferase (TdT) have nucleotide insertions at S-S junctions, indicating that the recombining DNA ends are accessible to end-processing enzyme activities.
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