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dc.contributor.authorSchrader, Carol E.
dc.contributor.authorLinehan, Erin K.
dc.contributor.authorMochegova, Sofia N.
dc.contributor.authorWoodland, Robert T.
dc.contributor.authorStavnezer, Janet
dc.date2022-08-11T08:11:04.000
dc.date.accessioned2022-08-23T17:31:04Z
dc.date.available2022-08-23T17:31:04Z
dc.date.issued2005-08-15
dc.date.submitted2007-09-14
dc.identifier.citation<p>J Exp Med. 2005 Aug 15;202(4):561-8. <a href="http://dx.doi.org/10.1084/jem.20050872">Link to article on publisher's site</a></p>
dc.identifier.issn0022-1007 (Print)
dc.identifier.doi10.1084/jem.20050872
dc.identifier.pmid16103411
dc.identifier.urihttp://hdl.handle.net/20.500.14038/50647
dc.description.abstractClass switch recombination (CSR) occurs by an intrachromosomal deletion whereby the IgM constant region gene (Cmu) is replaced by a downstream constant region gene. This unique recombination event involves formation of double-strand breaks (DSBs) in immunoglobulin switch (S) regions, and requires activation-induced cytidine deaminase (AID), which converts cytosines to uracils. Repair of the uracils is proposed to lead to DNA breaks required for recombination. Uracil DNA glycosylase (UNG) is required for most CSR activity although its role is disputed. Here we use ligation-mediated PCR to detect DSBs in S regions in splenic B cells undergoing CSR. We find that the kinetics of DSB induction corresponds with AID expression, and that DSBs are AID- and UNG-dependent and occur preferentially at G:C basepairs in WRC/GYW AID hotspots. Our results indicate that AID attacks cytosines on both DNA strands, and staggered breaks are processed to blunt DSBs at the initiating ss break sites. We propose a model to explain the types of end-processing events observed.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16103411&dopt=Abstract">Link to article in PubMed</a></p>
dc.rightsPublisher PDF posted as allowed by the publisher's terms of use policy at: http://www.rupress.org/terms After the Initial Publication Period, RUP will grant to the public the non-exclusive right to copy, distribute, or display the Article under a Creative Commons Attribution-Noncommercial-Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode, or updates thereof.
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/
dc.subjectAnimals
dc.subjectB-Lymphocytes
dc.subjectCytidine Deaminase
dc.subjectDNA
dc.subjectDNA Glycosylases
dc.subjectGene Expression Regulation
dc.subjectGene Rearrangement, B-Lymphocyte
dc.subjectImmunoglobulin Constant Regions
dc.subjectImmunoglobulin mu-Chains
dc.subjectMice
dc.subjectMice, Mutant Strains
dc.subjectRecombination, Genetic
dc.subjectSomatic Hypermutation, Immunoglobulin
dc.subjectSpleen
dc.subjectUracil-DNA Glycosidase
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.subjectWomen's Studies
dc.titleInducible DNA breaks in Ig S regions are dependent on AID and UNG
dc.typeJournal Article
dc.source.journaltitleThe Journal of experimental medicine
dc.source.volume202
dc.source.issue4
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1172&amp;context=wfc_pp&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/wfc_pp/173
dc.identifier.contextkey367634
refterms.dateFOA2022-08-23T17:31:04Z
html.description.abstract<p>Class switch recombination (CSR) occurs by an intrachromosomal deletion whereby the IgM constant region gene (Cmu) is replaced by a downstream constant region gene. This unique recombination event involves formation of double-strand breaks (DSBs) in immunoglobulin switch (S) regions, and requires activation-induced cytidine deaminase (AID), which converts cytosines to uracils. Repair of the uracils is proposed to lead to DNA breaks required for recombination. Uracil DNA glycosylase (UNG) is required for most CSR activity although its role is disputed. Here we use ligation-mediated PCR to detect DSBs in S regions in splenic B cells undergoing CSR. We find that the kinetics of DSB induction corresponds with AID expression, and that DSBs are AID- and UNG-dependent and occur preferentially at G:C basepairs in WRC/GYW AID hotspots. Our results indicate that AID attacks cytosines on both DNA strands, and staggered breaks are processed to blunt DSBs at the initiating ss break sites. We propose a model to explain the types of end-processing events observed.</p>
dc.identifier.submissionpathwfc_pp/173
dc.contributor.departmentDepartment of Molecular Genetics and Microbiology
dc.source.pages561-8


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Publisher PDF posted as allowed by the publisher's terms of use policy at: http://www.rupress.org/terms After the Initial Publication Period, RUP will grant to the public the non-exclusive right to copy, distribute, or display the Article under a Creative Commons Attribution-Noncommercial-Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode, or updates thereof.
Except where otherwise noted, this item's license is described as Publisher PDF posted as allowed by the publisher's terms of use policy at: http://www.rupress.org/terms After the Initial Publication Period, RUP will grant to the public the non-exclusive right to copy, distribute, or display the Article under a Creative Commons Attribution-Noncommercial-Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode, or updates thereof.