Specific recruitment of protein kinase A to the immunoglobulin locus regulates class-switch recombination Journal Article


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"
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MSK Authors
  1. Bao Q Vuong
    9 Vuong
  2. Mieun Lee
    3 Lee
  3. Shaheen Kabir
    1 Kabir
  4. Cristina Irimia
    1 Irimia