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Inducible Dna Breaks In Ig S Regions Are Dependent On Aid And Ung, Carol E. Schrader, Erin K. Linehan, Sofia N. Mochegova, Robert T. Woodland, Janet Stavnezer Aug 2005

Inducible Dna Breaks In Ig S Regions Are Dependent On Aid And Ung, Carol E. Schrader, Erin K. Linehan, Sofia N. Mochegova, Robert T. Woodland, Janet Stavnezer

Women’s Health Research Faculty Publications

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 ...


Shifts In Targeting Of Class Switch Recombination Sites In Mice That Lack Mu Switch Region Tandem Repeats Or Msh2, Irene M. Min, Lisa R. Rothlein, Carol E. Schrader, Janet Stavnezer, Erik Selsing Jun 2005

Shifts In Targeting Of Class Switch Recombination Sites In Mice That Lack Mu Switch Region Tandem Repeats Or Msh2, Irene M. Min, Lisa R. Rothlein, Carol E. Schrader, Janet Stavnezer, Erik Selsing

Women’s Health Research Faculty Publications

The mechanisms that target class switch recombination (CSR) to antibody gene switch (S) regions are unknown. Analyses of switch site locations in wild-type mice and in mice that lack the Smu tandem repeats show shifts indicating that a 4-5-kb DNA domain (bounded upstream by the Imu promoter) is accessible for switching independent of Smu sequences. This CSR-accessible domain is reminiscent of the promoter-defined domains that target somatic hypermutation. Within the 4-5-kb CSR domain, the targeting of S site locations also depends on the Msh2 mismatch repair protein because Msh2-deficient mice show an increased focus of sites to the Smu tandem ...