Schrader, Carol E.Linehan, Erin K.Mochegova, Sofia N.Woodland, Robert T.Stavnezer, Janet2022-08-232022-08-232005-08-152007-09-14<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>0022-1007 (Print)10.1084/jem.2005087216103411https://hdl.handle.net/20.500.14038/50647Class 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.en-USPublisher 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.http://creativecommons.org/licenses/by-nc-sa/4.0/AnimalsB-LymphocytesCytidine DeaminaseDNADNA GlycosylasesGene Expression RegulationGene Rearrangement, B-LymphocyteImmunoglobulin Constant RegionsImmunoglobulin mu-ChainsMiceMice, Mutant StrainsRecombination, GeneticSomatic Hypermutation, ImmunoglobulinSpleenUracil-DNA GlycosidaseLife SciencesMedicine and Health SciencesWomen's StudiesJournal Articlehttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1172&amp;context=wfc_pp&amp;unstamped=1https://escholarship.umassmed.edu/wfc_pp/173367634wfc_pp/173