| First Author | Pérez-Durán P | Year | 2012 |
| Journal | J Exp Med | Volume | 209 |
| Issue | 7 | Pages | 1379-89 |
| PubMed ID | 22665573 | Mgi Jnum | J:189103 |
| Mgi Id | MGI:5444348 | Doi | 10.1084/jem.20112253 |
| Citation | Perez-Duran P, et al. (2012) UNG shapes the specificity of AID-induced somatic hypermutation. J Exp Med 209(7):1379-89 |
| abstractText | Secondary diversification of antibodies through somatic hypermutation (SHM) and class switch recombination (CSR) is a critical component of the immune response. Activation-induced deaminase (AID) initiates both processes by deaminating cytosine residues in immunoglobulin genes. The resulting U:G mismatch can be processed by alternative pathways to give rise to a mutation (SHM) or a DNA double-strand break (CSR). Central to this processing is the activity of uracil-N-glycosylase (UNG), an enzyme normally involved in error-free base excision repair. We used next generation sequencing to analyze the contribution of UNG to the resolution of AID-induced lesions. Loss- and gain-of-function experiments showed that UNG activity can promote both error-prone and high fidelity repair of U:G lesions. Unexpectedly, the balance between these alternative outcomes was influenced by the sequence context of the deaminated cytosine, with individual hotspots exhibiting higher susceptibility to UNG-triggered error-free or error-prone resolution. These results reveal UNG as a new molecular layer that shapes the specificity of AID-induced mutations and may provide new insights into the role of AID in cancer development. |
