Rad52 mediates class-switch DNA recombination to IgD.

ABSTRACT: In B cells, IgD is expressed together with IgM through alternative splicing of primary V_HDJ_H-Cμ-s-m-Cδ-s-m RNAs, and also through IgD class switch DNA recombination (CSR) via double-strand DNA breaks (DSB) and synapse of Sμ with σδ. How such DSBs are resolved is still unknown, despite our previous report showing that Rad52 effects the 'short-range' microhomology-mediated synapsis of intra-Sμ region DSBs. Here we find that induction of IgD CSR downregulates Zfp318, and promotes Rad52 phosphorylation and recruitment to Sμ and σδ, thereby leading to alternative end-joining (A-EJ)-mediated Sμ-σδ recombination with extensive microhomologies, V_HDJ_H-Cδs transcription and sustained IgD secretion. Rad52 ablation in mouse Rad52^-/- B cells aborts

SUBMITTER: Xu Y 

PROVIDER: S-EPMC8861003 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature