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dc.contributor.authorRanjit, Sanjay
dc.contributor.authorKhair, Lyne
dc.contributor.authorLinehan, Erin K.
dc.contributor.authorUcher, Anna J.
dc.contributor.authorChakrabarti, Mrinmay
dc.contributor.authorSchrader, Carol E.
dc.contributor.authorStavnezer, Janet
dc.date2022-08-11T08:09:18.000
dc.date.accessioned2022-08-23T16:26:02Z
dc.date.available2022-08-23T16:26:02Z
dc.date.issued2011-09-01
dc.date.submitted2013-02-04
dc.identifier.citation<p>J Immunol. 2011 Sep 1;187(5):2464-75. doi: 10.4049/jimmunol.1101406. <a href="http://dx.doi.org/10.4049/jimmunol.1101406" target="_blank">Link to article on publisher's site</a></p>
dc.identifier.issn0022-1767 (Linking)
dc.identifier.doi10.4049/jimmunol.1101406
dc.identifier.pmid21804017
dc.identifier.urihttp://hdl.handle.net/20.500.14038/36476
dc.description.abstractActivation-induced cytidine deaminase (AID) is induced in B cells during an immune response and is essential for both class-switch recombination (CSR) and somatic hypermutation of Ab genes. The C-terminal 10 aa of AID are required for CSR but not for somatic hypermutation, although their role in CSR is unknown. Using retroviral transduction into mouse splenic B cells, we show that the C terminus is not required for switch (S) region double-strand breaks (DSBs) and therefore functions downstream of DSBs. Using chromatin immunoprecipitation, we show that AID binds cooperatively with UNG and the mismatch repair proteins Msh2-Msh6 to Ig Smu and Sgamma3 regions, and this depends on the C terminus and the deaminase activity of AID. We also show that mismatch repair does not contribute to the efficiency of CSR in the absence of the AID C terminus. Although it has been demonstrated that both UNG and Msh2-Msh6 are important for introduction of S region DSBs, our data suggest that the ability of AID to recruit these proteins is important for DSB resolution, perhaps by directing the S region DSBs toward accurate and efficient CSR via nonhomologous end joining.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=21804017&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3159830/pdf/nihms-307058.pdf
dc.subjectAnimals
dc.subjectB-Lymphocytes
dc.subjectCell Separation
dc.subjectChromatin Immunoprecipitation
dc.subjectCytidine Deaminase
dc.subjectDNA-Binding Proteins
dc.subjectFlow Cytometry
dc.subjectImmunoglobulin Class Switching
dc.subjectImmunoglobulin G
dc.subjectImmunoglobulin Switch Region
dc.subjectMice
dc.subjectMice, Inbred C57BL
dc.subjectMice, Knockout
dc.subjectMutS Homolog 2 Protein
dc.subjectProtein Binding
dc.subjectReverse Transcriptase Polymerase Chain Reaction
dc.subjectUracil-DNA Glycosidase
dc.subjectGenetics and Genomics
dc.subjectImmunology and Infectious Disease
dc.titleAID binds cooperatively with UNG and Msh2-Msh6 to Ig switch regions dependent upon the AID C terminus
dc.typeJournal Article
dc.source.journaltitleJournal of immunology (Baltimore, Md. : 1950)
dc.source.volume187
dc.source.issue5
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/maps_pubs/4
dc.identifier.contextkey3647921
html.description.abstract<p>Activation-induced cytidine deaminase (AID) is induced in B cells during an immune response and is essential for both class-switch recombination (CSR) and somatic hypermutation of Ab genes. The C-terminal 10 aa of AID are required for CSR but not for somatic hypermutation, although their role in CSR is unknown. Using retroviral transduction into mouse splenic B cells, we show that the C terminus is not required for switch (S) region double-strand breaks (DSBs) and therefore functions downstream of DSBs. Using chromatin immunoprecipitation, we show that AID binds cooperatively with UNG and the mismatch repair proteins Msh2-Msh6 to Ig Smu and Sgamma3 regions, and this depends on the C terminus and the deaminase activity of AID. We also show that mismatch repair does not contribute to the efficiency of CSR in the absence of the AID C terminus. Although it has been demonstrated that both UNG and Msh2-Msh6 are important for introduction of S region DSBs, our data suggest that the ability of AID to recruit these proteins is important for DSB resolution, perhaps by directing the S region DSBs toward accurate and efficient CSR via nonhomologous end joining.</p>
dc.identifier.submissionpathmaps_pubs/4
dc.contributor.departmentDepartment of Microbiology and Physiological Systems
dc.source.pages2464-75


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