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J. Biol. Chem., Vol. 282, Issue 35, 25308-25313, August 31, 2007

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Activation-induced Cytidine Deaminase-mediated Sequence Diversification Is Transiently Targeted to Newly Integrated DNA Substrates^*

Shu Yuan Yang, Sebastian D. Fugmann¹, Hillary S. Gramlich^¶2, and David G. Schatz³

From the Department of Immunobiology and ^¶Department of Cell Biology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06520-8011

The molecular features that allow activation-induced cytidine deaminase (AID) to target Ig and certain non-Ig genes are not understood, although transcription has been implicated as one important parameter. We explored this issue by testing the mutability of a non-Ig transcription cassette in Ig and non-Ig loci of the chicken B cell line DT40. The cassette did not act as a stable long term mutation target but was able to be mutated in an AID-dependent manner for a limited time post-integration. This indicates that newly integrated DNA has molecular characteristics that render it susceptible to modification by AID, with implications for how targeting and mis-targeting of AID occurs.

Received for publication, May 22, 2007 , and in revised form, July 3, 2007.

^* This work was supported in part by Grant AI066130 from the National Institutes of Health (to D. G. S.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Fig. S1.

¹ Supported by the Irvington Institute for Immunological Research. Present address: NIA, National Institutes of Health, 5600 Nathan Shock Dr., Baltimore, MD 21224.

² Supported by a National Science Foundation predoctoral fellowship.

³ An investigator of the Howard Hughes Medical Institute. To whom correspondence should be addressed: 300 Cedar St., Box 208011, New Haven, CT 06520-8011. Tel.: 203-737-2255; Fax: 203-785-3855; E-mail: david.schatz{at}yale.edu.

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