Title

AID binds cooperatively with UNG and Msh2-Msh6 to Ig switch regions dependent upon the AID C terminus

UMMS Affiliation

Department of Microbiology and Physiological Systems

Date

9-1-2011

Document Type

Article

Medical Subject Headings

Animals; B-Lymphocytes; Cell Separation; Chromatin Immunoprecipitation; Cytidine Deaminase; DNA-Binding Proteins; Flow Cytometry; Immunoglobulin Class Switching; Immunoglobulin G; Immunoglobulin Switch Region; Mice; Mice, Inbred C57BL; Mice, Knockout; MutS Homolog 2 Protein; Protein Binding; Reverse Transcriptase Polymerase Chain Reaction; Uracil-DNA Glycosidase

Disciplines

Genetics and Genomics | Immunology and Infectious Disease

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 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.

Comments

Citation: J Immunol. 2011 Sep 1;187(5):2464-75. doi: 10.4049/jimmunol.1101406. Link to article on publisher's site

Related Resources

Link to Article in PubMed

PubMed ID

21804017