Molecular mechanisms of DNA lesion and repair during antibody somatic hypermutation  

作　　者：Qian Hao Jinfeng Li Leng-Siew Yeap 

机构地区：[1]Shanghai Institute of Immunology,Department of Immunology and Microbiology,State Key Laboratory of Oncogenes and Related Genes,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China [2]Center for Immune-Related Diseases at Shanghai Institute of Immunology,Department of Endocrinology and Metabolic Diseases,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China

出　　处：《Science China(Life Sciences)》2024年第11期2344-2353,共10页中国科学（生命科学英文版）

基　　金：supported by the National Key Research and Development Program of China(2021YFA1301400);the National Natural Science Foundation of China(32370934);the Shanghai Jiao Tong University 2030 Initiative(2030-B23).

摘　　要：Antibody diversification is essential for an effective immune response,with somatic hypermutation(SHM)serving as a key molecular process in this adaptation.Activation-induced cytidine deaminase(AID)initiates SHM by inducing DNA lesions,which are ultimately resolved into point mutations,as well as small insertions and deletions(indels).These mutational outcomes contribute to antibody affinity maturation.The mechanisms responsible for generating point mutations and indels involve the base excision repair(BER)and mismatch repair(MMR)pathways,which are well coordinated to maintain genomic integrity while allowing for beneficial mutations to occur.In this regard,translesion synthesis(TLS)polymerases contribute to the diversity of mutational outcomes in antibody genes by enabling the bypass of DNA lesions.This review summarizes our current understanding of the distinct molecular mechanisms that generate point mutations and indels during SHM.Understanding these mechanisms is critical for elucidating the development of broadly neutralizing antibodies(bnAbs)and autoantibodies,and has implications for vaccine design and therapeutics.

关 键 词：somatic hypermutation(SHM) insertions and deletions(indels) AID base excision repair(BER) mismatch repair(MMR) translesion synthesis(TLS)polymerases 

分 类 号：Q754[生物学—分子生物学]