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Review
. 2021;2(2):115-125.
doi: 10.1007/s42764-021-00035-0. Epub 2021 Mar 26.

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

Yafang Shang  1 , Fei-Long Meng  1
Affiliations
Review

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

Yafang Shang et al. Genome Instab Dis. 2021.

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: AID; Class switch recombination; DNA repair; Deletional recombination; ERCC6L2; NHEJ; Rev7; Shieldin.

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Conflict of interest statement

Conflict of interestThe authors declare no competing financial interests.

Figures

Fig. 1
Fig. 1
IgH class switch recombination (CSR). Schematic illustration of IgH constant genes and AID targeting (a), processing of U’s into DSBs by BER and MMR (b), activation of DSBR (c) and end ligation by c-NHEJ and Alt-EJ (d). See text for more details
Fig. 2
Fig. 2
Multiple roles of Rev7 in CSR. Rev7 is involved in DSB response, transversion mutation, and toleration of AID-initiated AP sites in CSR. See text for more details
Fig. 3
Fig. 3
ERCC6L2-depedent deletional CSR. A working model to explain the molecular basis for deletional CSR. See text for more details
See this image and copyright information in PMC

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