A DNA break- and phosphorylation-dependent positive feedback loop promotes immunoglobulin class-switch recombination Journal Article
| Authors: | Vuong, B. Q.; Herrick-Reynolds, K.; Vaidyanathan, B.; Pucella, J. N.; Ucher, A. J.; Donghia, N. M.; Gu, X.; Nicolas, L.; Nowak, U.; Rahman, N.; Strout, M. P.; Mills, K. D.; Stavnezer, J.; Chaudhuri, J. |
| Article Title: | A DNA break- and phosphorylation-dependent positive feedback loop promotes immunoglobulin class-switch recombination |
| 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. © 2013 Nature America, Inc. |
| Keywords: | controlled study; unclassified drug; nonhuman; animal cell; mouse; protein protein interaction; protein; dna strand breakage; activation induced cytidine deaminase; immunoglobulin heavy chain; enzyme phosphorylation; gene rearrangement; genetic recombination; atm protein; endonuclease; positive feedback; protein ape1 |
| Journal Title: | Nature Immunology |
| Volume: | 14 |
| Issue: | 11 |
| ISSN: | 1529-2908 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2013-11-01 |
| Start Page: | 1183 |
| End Page: | 1189 |
| Language: | English |
| DOI: | 10.1038/ni.2732 |
| PROVIDER: | scopus |
| PUBMED: | 24097111 |
| PMCID: | PMC4005274 |
| DOI/URL: | |
| Notes: | --- - Cited By (since 1996):1 - "Export Date: 2 December 2013" - "CODEN: NIAMC" - "Source: Scopus" |
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