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J. Biol. Chem., Vol. 280, Issue 25, 23593-23598, June 24, 2005

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Direct DNA Binding Activity of the Fanconi Anemia D2 Protein^*

Woo-Hyun Park, Steven Margossian¶, Andrew A. Horwitz, Amanda M. Simons, Alan D. D'Andrea, and Jeffrey D. Parvin||

From the Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, the Departments of Pediatric Oncology and Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, and the ^¶Division of Hematology/Oncology, Children's Hospital, Boston, Massachusetts 02115

It is known that the Fanconi anemia D2 protein is vital for protecting the genome from DNA damage, but what activities this protein has are unknown. In these experiments we purified full-length Fanconi anemia protein D2 (FANCD2), and we found that FANCD2 bound to DNA with specificity for certain structures: double strand DNA ends and Holliday junctions. Proteins containing patient-derived mutations or artificial variants of the FANCD2 protein were similarly expressed and purified, and each variant bound to the Holliday junction DNA with similar affinity as did the wild-type protein. There was no single discrete domain of FANCD2 protein that bound to DNA, but rather the full-length protein was required for structure-specific DNA binding. This finding of DNA binding is the first biochemical activity identified for this key protein in the Fanconi anemia pathway.

Received for publication, April 5, 2005 , and in revised form, April 20, 2005.

^* This work was supported by a postdoctoral fellowship (to W.-H. P.) and a predoctoral fellowship (to A. A. H.) from the Department of Defense Breast Cancer Research Program, a predoctoral fellowship from the National Science Foundation (to A. M. S.), the David Abraham Fellowship (to S. M.), and Research Grant CA090281 from the NCI/National Institutes of Health (to J. D. P.). 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 Figs. S1 and S2.

^|| To whom correspondence should be addressed. E-mail: JParvin{at}rics.bwh.harvard.edu.

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