DNA double strand breaks occur independent of AID in hypermutating Ig genes.

Somatic hypermutation (SHM) and class switch recombination (CSR) take place in B cells of the germinal center (GC) and are associated with DNA double-strand breaks (DNA-DSBs). Transcription favors the generation of DNA-DSBs in the V-regions and switch regions of Ig genes. Both SHM and CSR are controlled by the Activation Induced Cytidine Deaminase (AID), an enzyme exclusively expressed in B cells of the GC.

Somatic hypermutation does not require Rad54 and Rad54B-mediated homologous recombination.

Secondary diversification of immunoglobulin (Ig) genes occurs through somatic hypermutation (SHM) in B cells of the germinal center (GC). The GC reaction is associated with a high frequency of DNA double-strand breaks (DSB) in the hypermutation domain of Ig genes. Homologous recombination (HR) is a prominent DSB repair pathway.

DNA double-strand breaks: prior to but not sufficient in targeting hypermutation.

The activation-induced cytidine deaminase (AID) is required for somatic hypermutation (SHM) and class-switch recombination (CSR) of immunoglobulin (Ig) genes, both of which are associated with DNA double-strand breaks (DSBs). As AID is capable of deaminating deoxy-cytidine (dC) to deoxy-uracil (dU), it might induce nicks (single strand DNA breaks) and also DNA DSBs via a U-DNA glycosylase-mediated base excision repair pathway ('DNA-substrate model'). Alternatively, AID functions like its closest homologue Apobec1 as a catalytic subunit of a RNA editing holoenzyme ('RNA-substrate model').