Authors: | Vuong, B. Q.; Lee, M.; Kabir, S.; Irimia, C.; Macchiarulo, S.; McKnight, G. S.; Chaudhuri, J. |
Article Title: | Specific recruitment of protein kinase A to the immunoglobulin locus regulates class-switch recombination |
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. |
Keywords: | controlled study; protein expression; gene mutation; nonhuman; animal cell; mouse; animals; mice; mice, mutant strains; protein binding; gene locus; immunoglobulin; enzyme activation; phosphorylation; deamination; enzyme phosphorylation; gene rearrangement; genetic recombination; cytidine deaminase; recombination, genetic; dna breaks, double-stranded; double stranded dna break; catalysis; immunoglobulin class switching; enzyme subunit; replication protein a; gene replication; cyclic amp dependent protein kinase; cyclic amp-dependent protein kinases; retroviridae infections |
Journal Title: | Nature Immunology |
Volume: | 10 |
Issue: | 4 |
ISSN: | 1529-2908 |
Publisher: | Nature Publishing Group |
Date Published: | 2009-04-01 |
Start Page: | 420 |
End Page: | 426 |
Language: | English |
DOI: | 10.1038/ni.1708 |
PUBMED: | 19234474 |
PROVIDER: | scopus |
PMCID: | PMC4169875 |
DOI/URL: | |
Notes: | --- - "Cited By (since 1996): 9" - "Export Date: 30 November 2010" - "CODEN: NIAMC" - "Source: Scopus" |