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dc.contributor.authorSchrader, Carol E.
dc.contributor.authorBradley, Sean P.
dc.contributor.authorVardo, Joycelyn
dc.contributor.authorMochegova, Sofia N.
dc.contributor.authorFlanagan, Erin
dc.contributor.authorStavnezer, Janet
dc.date2022-08-11T08:11:04.000
dc.date.accessioned2022-08-23T17:31:05Z
dc.date.available2022-08-23T17:31:05Z
dc.date.issued2003-11-01
dc.date.submitted2007-09-14
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.issn0261-4189 (Print)
dc.identifier.doi10.1093/emboj/cdg550
dc.identifier.pmid14592986
dc.identifier.urihttp://hdl.handle.net/20.500.14038/50653
dc.description.abstractNucleotide 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.isoen_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.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC275407/
dc.subjectAnimals
dc.subjectB-Lymphocytes
dc.subjectBase Composition
dc.subjectBase Sequence
dc.subjectDNA
dc.subjectDNA Nucleotidylexotransferase
dc.subjectDNA Repair
dc.subject*DNA-Binding Proteins
dc.subject*Immunoglobulin Switch Region
dc.subjectLymphocyte Activation
dc.subjectMice
dc.subjectMice, Knockout
dc.subjectMice, Transgenic
dc.subjectMolecular Sequence Data
dc.subjectMutS Homolog 2 Protein
dc.subject*Mutation
dc.subjectProto-Oncogene Proteins
dc.subjectRecombinant Proteins
dc.subject*Recombination, Genetic
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.subjectWomen's Studies
dc.titleMutations occur in the Ig Smu region but rarely in Sgamma regions prior to class switch recombination
dc.typeJournal Article
dc.source.journaltitleThe EMBO journal
dc.source.volume22
dc.source.issue21
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/wfc_pp/179
dc.identifier.contextkey367640
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.submissionpathwfc_pp/179
dc.contributor.departmentDepartment of Molecular Genetics and Microbiology
dc.source.pages5893-903


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