Zarrin Ali A, Del Vecchio Catherine, Tseng Eva, Gleason Megan, Zarin Payam, Tian Ming, Alt Frederick W
Howard Hughes Medical Institute, Children's Hospital, CBR Institute for Biomedical Research, and Department of Genetics, Harvard University Medical School, Boston, MA 02115, USA.
Science. 2007 Jan 19;315(5810):377-81. doi: 10.1126/science.1136386. Epub 2006 Dec 14.
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 Smu and accepter Sgamma1 regions were replaced with yeast I-SceI endonuclease sites. We found that site-specific I-SceI DSBs mediate recombinational IgH locus class switching from IgM to IgG1 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.
活化B细胞中的抗体类别转换利用类别转换重组（CSR），该过程将两个位于相距达200千碱基的大型免疫球蛋白重链（IgH）基因座转换（S）区域内依赖于活化诱导的胞苷脱氨酶（AID）的双链断裂（DSB）连接起来。为了测试S区域和AID在CSR中的假定作用，我们生成了突变B细胞，其中供体Smu和受体Sgamma1区域被酵母I-SceI内切酶位点取代。我们发现，位点特异性I-SceI DSB可介导重组IgH基因座类别从IgM转换为IgG1，而无需S区域或AID。我们提出，CSR的进化是为了利用一种促进染色体内广泛分离的DSB连接的一般DNA修复过程。
