Article abstract
Nature Immunology 10, 420 - 426 (2009)
Published online: 22 February 2009 | doi:10.1038/ni.1708
Specific recruitment of protein kinase A to the immunoglobulin locus regulates class-switch recombination
Bao Q Vuong1, Mieun Lee1, Shaheen Kabir1, Cristina Irimia1,2, Stephania Macchiarulo1, G Stanley McKnight3 & Jayanta Chaudhuri1,2
Abstract
Immunoglobulin class-switch recombination (CSR) requires activation-induced cytidine deaminase (AID). Deamination of DNA by AID in transcribed switch (S) regions leads to double-stranded breaks in DNA that serve as obligatory CSR intermediates. Here we demonstrate that the catalytic and regulatory subunits of protein kinase A (PKA) were specifically recruited to S regions to promote the localized phosphorylation of AID, which led to binding of replication protein A and subsequent propagation of the CSR cascade. Accordingly, inactivation of PKA resulted in considerable disruption of CSR because of decreased AID phosphorylation and recruitment of replication protein A to S regions. We propose that PKA nucleates the formation of active AID complexes specifically on S regions to generate the high density of DNA lesions required for CSR.
- Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
- Gerstner Sloan-Kettering Graduate School of Biomedical Sciences, New York, New York, USA.
- Department of Pharmacology, University of Washington, Seattle, Washington, USA.
Correspondence to: Jayanta Chaudhuri1,2 e-mail: chaudhuj@mskcc.org
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