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Originally published In Press as doi:10.1074/jbc.M300770200 on March 11, 2003

J. Biol. Chem., Vol. 278, Issue 20, 17655-17663, May 16, 2003
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Chromatin Remodeling Activities Act on UV-damaged Nucleosomes and Modulate DNA Damage Accessibility to Photolyase*

Hélène GaillardDagger §, Daniel J. Fitzgerald, Corey L. Smith||, Craig L. Peterson||, Timothy J. Richmond, and Fritz ThomaDagger **

From the Dagger  Institut für Zellbiologie and  Institut für Molekularbiologie, Departement Biologie, ETH-Hönggerberg, CH-8093 Zürich, Switzerland and || Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605

Nucleosomes inhibit DNA repair in vitro, suggesting that chromatin remodeling activities might be required for efficient repair in vivo. To investigate how structural and dynamic properties of nucleosomes affect damage recognition and processing, we investigated repair of UV lesions by photolyase on a nucleosome positioned at one end of a 226-bp-long DNA fragment. Repair was slow in the nucleosome but efficient outside. No disruption or movement of the nucleosome was observed after UV irradiation and during repair. However, incubation with the nucleosome remodeling complex SWI/SNF and ATP altered the conformation of nucleosomal DNA as judged by UV photo-footprinting and promoted more homogeneous repair. Incubation with yISW2 and ATP moved the nucleosome to a more central position, thereby altering the repair pattern. This is the first demonstration that two different chromatin remodeling complexes can act on UV-damaged nucleosomes and modulate repair. Similar activities might relieve the inhibitory effect of nucleosomes on DNA repair processes in living cells.


* This work was supported by grants from the Swiss National Science Foundation, the ETH Zürich, and the Roche Research Foundation.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ Present address: Dept. de Genética, Facultad de Biología, Universidad de Sevilla, Avenida Reina Mercedes 6, 41012 Sevilla, Spain.

** To whom correspondence should be addressed: Institut für Zellbiologie, ETH-Hönggerberg, CH-8093 Zürich, Switzerland. Tel.: 41-1-633 33 23; Fax: 41-1-633 10 69; E-mail: thoma@cell.biol.ethz.ch.


Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
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