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Originally published in Science Express on 14 December 2006
Science 19 January 2007:
Vol. 315. no. 5810, pp. 377 - 381
DOI: 10.1126/science.1136386
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Reports

Antibody Class Switching Mediated by Yeast Endonuclease-Generated DNA Breaks

Ali A. Zarrin,1 Catherine Del Vecchio,1 Eva Tseng,1 Megan Gleason,1 Payam Zarin,1 Ming Tian,2 Frederick W. Alt1*

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 Sµ and accepter S{gamma}1 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.

1 Howard Hughes Medical Institute, Children's Hospital, CBR Institute for Biomedical Research, and Department of Genetics, Harvard University Medical School, Boston, MA 02115, USA.
2 Department of Molecular Genetics and Microbiology, University of Texas at Austin, Austin, TX 78712, USA.

* To whom correspondence should be addressed. E-mail: alt{at}enders.tch.harvard.edu

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From the Cover: Antisense transcripts from immunoglobulin heavy-chain locus V(D)J and switch regions.
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