Antibody class switching mediated by yeast endonuclease-generated DNA breaks

被引:77
作者
Zarrin, Ali A.
Del Vecchio, Catherine
Tseng, Eva
Gleason, Megan
Zarin, Payam
Tian, Ming
Alt, Frederick W. [1 ]
机构
[1] Harvard Univ, Sch Med, Childrens Hosp, CBR Inst Biomed Res,Howard Hughes Med Inst, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA
[3] Univ Texas, Dept Mol Genet & Microbiol, Austin, TX 78712 USA
关键词
D O I
10.1126/science.1136386
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Antibody class switching in activated B cells uses class switch recombination (CSR), which joins activation-induced cytidine deaminase (AID)-dependent double-strand breaks (DSBs) within two large immunoglobulin heavy chain (IgH) locus switch (S) regions that lie up to 200 kilobases apart. To test postulated roles of S regions and AID in CSR, we generated mutant B cells in which donor S mu and accepter S gamma 1 regions were replaced with yeast 1-SceI endonuclease sites. We found that site-specific 1-SceI DSBs mediate recombinational IgH locus class switching from IgM to IgG(2) without S regions or AID. We propose that CSR evolved to exploit a general DNA repair process that promotes joining of widely separated DSBs within a chromosome.
引用
收藏
页码:377 / 381
页数:5
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