2026-06-14T06:44:17Zhttps://repisalud.isciii.es/rest/oai/requestoai: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
Repisalud
author
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
funder
Ministerio de Educación, Cultura y Deporte (España)
funder
Ministerio de Economía, Industria y Competitividad (España)
funder
Unión Europea. Comisión Europea
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
funder
Fundación ProCNIC
2018-10-26T07:59:28Z
2018-10-26T07:59:28Z
2018
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
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.
eng
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
journal article
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ABbroadAtlasOfSomatic _2018.pdf
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ABbroadAtlasOfSomatic _2018.pdf.txt