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Vol. 19, Issue 7, 2926-2935, July 2008

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Rad54B Targeting to DNA Double-Strand Break Repair Sites Requires Complex Formation with S100A11

Ulrike Murzik^*, Peter Hemmerich, Stefanie Weidtkamp-Peters^,, Tobias Ulbricht, Wendy Bussen^,||, Julia Hentschel^*, Ferdinand von Eggeling^*, and Christian Melle^*

*Core Unit Chip Application (CUCA), Institute of Human Genetics and Anthropology, Medical Faculty, Friedrich-Schiller-University, 07740 Jena, Germany; Department of Molecular Biology, Fritz Lipmann Institut (FLI), Leibniz Institute for Age Research, 07708 Jena, Germany; and Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06515

Submitted November 20, 2007; Revised March 14, 2008; Accepted April 24, 2008
Monitoring Editor: M. Bishr Omary

S100A11 is involved in a variety of intracellular activities such as growth regulation and differentiation. To gain more insight into the physiological role of endogenously expressed S100A11, we used a proteomic approach to detect and identify interacting proteins in vivo. Hereby, we were able to detect a specific interaction between S100A11 and Rad54B, which could be confirmed under in vivo conditions. Rad54B, a DNA-dependent ATPase, is described to be involved in recombinational repair of DNA damage, including DNA double-strand breaks (DSBs). Treatment with bleomycin, which induces DSBs, revealed an increase in the degree of colocalization between S100A11 and Rad54B. Furthermore, S100A11/Rad54B foci are spatially associated with sites of DNA DSB repair. Furthermore, while the expression of p21^WAF1/CIP1 was increased in parallel with DNA damage, its protein level was drastically down-regulated in damaged cells after S100A11 knockdown. Down-regulation of S100A11 by RNA interference also abolished Rad54B targeting to DSBs. Additionally, S100A11 down-regulated HaCaT cells showed a restricted proliferation capacity and an increase of the apoptotic cell fraction. These observations suggest that S100A11 targets Rad54B to sites of DNA DSB repair sites and identify a novel function for S100A11 in p21-based regulation of cell cycle.

Present addresses: Lehrstuhl für Molekulare Physikalische Chemie, Institut für Physikalische Chemie, Heinrich-Heine-Universität Düsseldorf, 40225 Düsseldorf, Germany;

^|| Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO 63108.

Address correspondence to: Christian Melle (christian.melle{at}mti.uni-jena.de)