A DNA break- and phosphorylation-dependent positive feedback loop promotes immunoglobulin class-switch recombination.
Document Type
Article
Publication Date
11-2013
JAX Source
Nat Immunol 2013 Nov; 14(11):1183-9.
Volume
14
Issue
11
First Page
1183
Last Page
1189
ISSN
1529-2916
PMID
24097111
Abstract
The ability of activation-induced cytidine deaminase (AID) to efficiently mediate class-switch recombination (CSR) is dependent on its phosphorylation at Ser38; however, the trigger that induces AID phosphorylation and the mechanism by which phosphorylated AID drives CSR have not been elucidated. Here we found that phosphorylation of AID at Ser38 was induced by DNA breaks. Conversely, in the absence of AID phosphorylation, DNA breaks were not efficiently generated at switch (S) regions in the immunoglobulin heavy-chain locus (Igh), consistent with a failure of AID to interact with the endonuclease APE1. Additionally, deficiency in the DNA-damage sensor ATM impaired the phosphorylation of AID at Ser38 and the interaction of AID with APE1. Our results identify a positive feedback loop for the amplification of DNA breaks at S regions through the phosphorylation- and ATM-dependent interaction of AID with APE1. Nat Immunol 2013 Nov; 14(11):1183-9.
Recommended Citation
Vuong B,
Herrick-Reynolds K,
Vaidyanathan B,
Pucella J,
Ucher A,
Donghia NM,
Gu X,
Nicolas L,
Nowak U,
Rahman N,
Strout M,
Mills KD,
Stavnezer J,
Chaudhuri J.
A DNA break- and phosphorylation-dependent positive feedback loop promotes immunoglobulin class-switch recombination. Nat Immunol 2013 Nov; 14(11):1183-9.