Repair of programmed DNA lesions in antibody class switch recombination: common and unique features

Abstract

The adaptive immune system can diversify the antigen receptors to eliminate various pathogens through programmed DNA lesions at antigen receptor genes. In immune diversification, general DNA repair machineries are applied to transform the programmed DNA lesions into gene mutation or recombination events with common and unique features. Here we focus on antibody class switch recombination (CSR), and review the initiation of base damages, the conversion of damaged base to DNA double-strand break, and the ligation of broken ends. With an emphasis on the unique features in CSR, we discuss recent advances in the understanding of DNA repair/replication coordination, and ERCC6L2-mediated deletional recombination. We further elaborate the application of CSR in end-joining, resection and translesion synthesis assays. In the time of the COVID-19 pandemic, we hope it help to understand the generation of therapeutic antibodies.

Keywords

DNA repair / Class switch recombination / NHEJ / AID / ERCC6L2 / Rev7 / Shieldin / Deletional recombination / Biological Sciences / Genetics / Medical and Health Sciences / Immunology

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Funding

Key Technologies Research and Development Program(2017YFA0506700)

National Natural Science Foundation of China(81622022)

Strategic Priority Research Program of Chinese Academy of Sciences(XDB19030000)

RIGHTS & PERMISSIONS

Shenzhen University School of Medicine; Fondazione Istituto FIRC di Oncologia Molecolare