First Author | Vuong BQ | Year | 2009 |
Journal | Nat Immunol | Volume | 10 |
Issue | 4 | Pages | 420-6 |
PubMed ID | 19234474 | Mgi Jnum | J:147785 |
Mgi Id | MGI:3842220 | Doi | 10.1038/ni.1708 |
Citation | Vuong BQ, et al. (2009) Specific recruitment of protein kinase A to the immunoglobulin locus regulates class-switch recombination. Nat Immunol 10(4):420-6 |
abstractText | 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. |