Genome

Antibody

Somatic hypermutation

DNA repair

Base excision repair

Somatic cell

Activation-induced (cytidine) deaminase

Gene

Biology

Cytidine deaminase

B cell

Genetics

Computational biology

Germinal center

The Journal of Experimental Medicine

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 &amp;gt;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 activ...

A broad atlas of somatic hypermutation allows prediction of activation-induced deaminase targets