| AID Binds Cooperatively with UNG and Msh2-Msh6 to Ig Switch Regions Dependent upon the AID C Terminus. | |
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MedLine Citation:
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PMID: 21804017 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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Sanjay Ranjit; Lyne Khair; Erin K Linehan; Anna J Ucher; Mrinmay Chakrabarti; Carol E Schrader; Janet Stavnezer |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-7-29 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: - ISSN: 1550-6606 ISO Abbreviation: - Publication Date: 2011 Jul |
Date Detail:
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Created Date: 2011-8-1 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01655. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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