AID binds cooperatively with UNG and Msh2-Msh6 to Ig switch regions dependent upon the AID C terminus
Linehan, Erin K.
Ucher, Anna J.
Schrader, Carol E.
UMass Chan AffiliationsDepartment of Microbiology and Physiological Systems
Document TypeJournal Article
Immunoglobulin Class Switching
Immunoglobulin Switch Region
Mice, Inbred C57BL
MutS Homolog 2 Protein
Reverse Transcriptase Polymerase Chain Reaction
Genetics and Genomics
Immunology and Infectious Disease
MetadataShow full item record
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.
J Immunol. 2011 Sep 1;187(5):2464-75. doi: 10.4049/jimmunol.1101406. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/36476
Related ResourcesLink to Article in PubMed