AID Binds Cooperatively with UNG and Msh2-Msh6 to Ig Switch Regions Dependent upon the AID C Terminus

• Published in: The Journal of immunology (1950) Vol. 187; no. 5; pp. 2464 - 2475
• Main Authors: Ranjit, Sanjay, Khair, Lyne, Linehan, Erin K., Ucher, Anna J., Chakrabarti, Mrinmay, Schrader, Carol E., Stavnezer, Janet
• Format: Journal Article
• Language: English
• Published: 01.09.2011
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1101406

Abstract 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 Sμ and Sγ3 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.