AID Binds Cooperatively with UNG and Msh2-Msh6 to Ig Switch Regions Dependent upon the AID C Terminus
| Autor: | Erin K. Linehan, Janet Stavnezer, Sanjay Ranjit, Anna J. Ucher, Carol E. Schrader, Lyne Khair, Mrinmay Chakrabarti |
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| Rok vydání: | 2011 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 187:2464-2475 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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