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

来源：

SCIENCE | 2007年 / 315卷 / 5810期

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.

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收藏

页码：377 / 381

页数：5

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