Schrader, Carol E.Bradley, Sean P.Vardo, JoycelynMochegova, Sofia N.Flanagan, ErinStavnezer, Janet2022-08-232022-08-232003-11-012007-09-14<p>EMBO J. 2003 Nov 3;22(21):5893-903. <a href="http://dx.doi.org/10.1093/emboj/cdg550">Link to article on publisher's site</a></p>0261-4189 (Print)10.1093/emboj/cdg55014592986https://hdl.handle.net/20.500.14038/50653Nucleotide substitutions are found in recombined Ig switch (S) regions and also in unrecombined (germline, GL) Smicro 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 Smicro segment and secondarily involves the downstream acceptor S region. Furthermore, the pattern and specificity of mutations in GL and recombined Smicro segments differ, suggesting different repair mechanisms. Mutations in recombined Smicro regions show a strong bias toward G/C base pairs and WRCY/RGYW hotspots, whereas mutations introduced into the GL Smicro do not. Additionally, induction conditions affect mutation specificity within the GL Smicro 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.en-USAnimalsB-LymphocytesBase CompositionBase SequenceDNADNA NucleotidylexotransferaseDNA Repair*DNA-Binding Proteins*Immunoglobulin Switch RegionLymphocyte ActivationMiceMice, KnockoutMice, TransgenicMolecular Sequence DataMutS Homolog 2 Protein*MutationProto-Oncogene ProteinsRecombinant Proteins*Recombination, GeneticLife SciencesMedicine and Health SciencesWomen's StudiesJournal Articlehttps://escholarship.umassmed.edu/wfc_pp/179367640wfc_pp/179