Mutations occur in the Ig Smu region but rarely in Sgamma regions prior to class switch recombination
dc.contributor.author | Schrader, Carol E. | |
dc.contributor.author | Bradley, Sean P. | |
dc.contributor.author | Vardo, Joycelyn | |
dc.contributor.author | Mochegova, Sofia N. | |
dc.contributor.author | Flanagan, Erin | |
dc.contributor.author | Stavnezer, Janet | |
dc.date | 2022-08-11T08:11:04.000 | |
dc.date.accessioned | 2022-08-23T17:31:05Z | |
dc.date.available | 2022-08-23T17:31:05Z | |
dc.date.issued | 2003-11-01 | |
dc.date.submitted | 2007-09-14 | |
dc.identifier.citation | <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> | |
dc.identifier.issn | 0261-4189 (Print) | |
dc.identifier.doi | 10.1093/emboj/cdg550 | |
dc.identifier.pmid | 14592986 | |
dc.identifier.uri | http://hdl.handle.net/20.500.14038/50653 | |
dc.description.abstract | Nucleotide 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. | |
dc.language.iso | en_US | |
dc.relation | <p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14592986&dopt=Abstract">Link to article in PubMed</a></p> | |
dc.relation.url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC275407/ | |
dc.subject | Animals | |
dc.subject | B-Lymphocytes | |
dc.subject | Base Composition | |
dc.subject | Base Sequence | |
dc.subject | DNA | |
dc.subject | DNA Nucleotidylexotransferase | |
dc.subject | DNA Repair | |
dc.subject | *DNA-Binding Proteins | |
dc.subject | *Immunoglobulin Switch Region | |
dc.subject | Lymphocyte Activation | |
dc.subject | Mice | |
dc.subject | Mice, Knockout | |
dc.subject | Mice, Transgenic | |
dc.subject | Molecular Sequence Data | |
dc.subject | MutS Homolog 2 Protein | |
dc.subject | *Mutation | |
dc.subject | Proto-Oncogene Proteins | |
dc.subject | Recombinant Proteins | |
dc.subject | *Recombination, Genetic | |
dc.subject | Life Sciences | |
dc.subject | Medicine and Health Sciences | |
dc.subject | Women's Studies | |
dc.title | Mutations occur in the Ig Smu region but rarely in Sgamma regions prior to class switch recombination | |
dc.type | Journal Article | |
dc.source.journaltitle | The EMBO journal | |
dc.source.volume | 22 | |
dc.source.issue | 21 | |
dc.identifier.legacycoverpage | https://escholarship.umassmed.edu/wfc_pp/179 | |
dc.identifier.contextkey | 367640 | |
html.description.abstract | <p>Nucleotide 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.</p> | |
dc.identifier.submissionpath | wfc_pp/179 | |
dc.contributor.department | Department of Molecular Genetics and Microbiology | |
dc.source.pages | 5893-903 |