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作 者:Wanyu Bai Bo Zhao Mingyu Gu Junchao Dong
机构地区:[1]Department of Immunology,Zhongshan School of Medicine,Sun Yat-sen University,Guangzhou 510080,China [2]Key Laboratory of Tropical Disease Control(Sun Yat-sen University),Ministry of Education,Guangzhou 510080,China
出 处:《Acta Biochimica et Biophysica Sinica》2022年第6期782-795,共14页生物化学与生物物理学报(英文版)
基 金:the grants from the National Natural Science Foundation of China(Nos.,81871304,32070892);Guangdong Innovative and Entrepreneurial Research Team Program(No.,2016ZT06S252);Guangzhou Municipal Science and Technology Bureau(No.,202002030064);the Fundamental Research Funds for the Central Universities(No.,18ykzd11);Sanming Project of Medicine in Shenzhen(No.,SZSM202011004);Open project of Key Laboratory of Tropical Disease Control(Sun,Yat-sen,University);Ministry of Education(No.,2020ZX01)。
摘 要:Programmed DNA double-strand breaks(DSBs)occur during antigen receptor gene recombination,namely V(D)J recombination in developing B lymphocytes and class switch recombination(CSR)in mature B cells.Repair of these DSBs by classical end-joining(c-NHEJ)enables the generation of diverse BCR repertoires for efficient humoral immunity.Deletion of or mutation in c-NHEJ genes in mice and humans confer various degrees of primary immune deficiency and predisposition to lymphoid malignancies that often harbor oncogenic chromosomal translocations.In the absence of c-NHEJ,alternative end-joining(A-EJ)catalyzes robust CSR and to a much lesser extent,V(D)J recombination,but the mechanisms of A-EJ are only poorly defined.In this review,we introduce recent advances in the understanding of A-EJ in the context of V(D)J recombination and CSR with emphases on DSB end processing,DNA polymerases and ligases,and discuss the implications of A-EJ to lymphoid development and chromosomal translocations.
关 键 词:classical nonhomologous end-joining alternative end-joining V(D)J recombination chromosomal translocation DSB end resection ENDONUCLEASE
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