2026-06-14T03:28:55Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/65452024-09-27T10:00:37Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605col_20.500.12105_19607

00925njm 22002777a 4500 dc Alvarez-Prado, Angel Francisco author Perez-Duran, Pablo author Perez-Garcia, Arantxa author Benguria, Alberto author Torroja, Carlos author de Yebenes, Virginia G author Ramiro, Almudena R author 2018 Activation-induced deaminase (AID) initiates antibody diversification in germinal center (GC) B cells through the deamination of cytosines on immunoglobulin genes. AID can also target other regions in the genome, triggering mutations or chromosome translocations, with major implications for oncogenic transformation. However, understanding the specificity of AID has proved extremely challenging. We have sequenced at very high depth > 1,500 genomic regions from GC B cells and identified 275 genes targeted by AID, including 30 of the previously known 35 AID targets. We have also identified the most highly mutated hotspot for AID activity described to date. Furthermore, integrative analysis of the molecular features of mutated genes coupled to machine learning has produced a powerful predictive tool for AID targets. We also have found that base excision repair and mismatch repair back up each other to faithfully repair AID-induced lesions. Finally, our data establish a novel link between AID mutagenic activity and lymphomagenesis. J Exp Med. 2018; 215(3):761-771 10.1084/jem.20171738 1540-9538 0022-1007 Journal of Experimental Medicine 29374026 http://hdl.handle.net/20.500.12105/6545 INDUCED CYTIDINE DEAMINASE B-CELL LYMPHOMAS CLASS SWITCH RECOMBINATION SEQUENCING REVEALS GENOMIC INSTABILITY SUPER-ENHANCERS DEFICIENT MICE DNA BREAKS IG GENES C-MYC A broad atlas of somatic hypermutation allows prediction of activation-induced deaminase targets