Journal
NATURE IMMUNOLOGY
Volume 10, Issue 4, Pages 420-426Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.1708
Keywords
-
Categories
Funding
- US National Institutes of Health [T32CA09149]
- Damon Runyon Cancer Research Foundation
- Bressler Scholars Foundation
- Frederick Adler Chair for Junior Faculty
- SloanKettering Institute
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available