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Recruitment of RNA polymerase II cofactor PC4 to DNA damage sites

¹ Department of Biology II, Ludwig Maximilians University Munich, 82152 Planegg-Martinsried, Germany
² Center for Integrated Protein Science Munich, 81377 Munich, Germany
³ Department of Gene Expression, Helmholtz Zentrum Munich-German Research Center for Environmental Health, 81377 Munich, Germany
⁴ Faculty of Medicine, Institute for Molecular Tumor Biology, Westphalian Wilhelms University Muenster, 48149 Muenster, Germany
⁵ Department of Biology, Technische Universität Darmstadt, 64289 Darmstadt, Germany

Correspondence to Heinrich Leonhardt: h.leonhardt{at}lmu.de

The multifunctional nuclear protein positive cofactor 4 (PC4) is involved in various cellular processes including transcription, replication, and chromatin organization. Recently, PC4 has been identified as a suppressor of oxidative mutagenesis in Escherichia coli and Saccharomyces cerevisiae. To investigate a potential role of PC4 in mammalian DNA repair, we used a combination of live cell microscopy, microirradiation, and fluorescence recovery after photobleaching analysis. We found a clear accumulation of endogenous PC4 at DNA damage sites introduced by either chemical agents or laser microirradiation. Using fluorescent fusion proteins and specific mutants, we demonstrated that the rapid recruitment of PC4 to laser-induced DNA damage sites is independent of poly(ADP-ribosyl)ation and H2AX but depends on its single strand binding capacity. Furthermore, PC4 showed a high turnover at DNA damages sites compared with the repair factors replication protein A and proliferating cell nuclear antigen. We propose that PC4 plays a role in the early response to DNA damage by recognizing single-stranded DNA and may thus initiate or facilitate the subsequent steps of DNA repair.

W. Roth's present address is Division of Cell Biochemistry, Institute of Physiological Chemistry, University of Bonn, 53115 Bonn, Germany.

Abbreviations used in this paper: Aph, aphidicolin; CK2, casein kinase II; CTD,C-terminal domain; HU, Hydroxyurea; MEF, mouse embryonic fibroblast; PAR, poly(ADP-ribose); PC4, positive cofactor 4; PCNA, proliferating cell nuclear antigen; RPA, replication protein A; ssDNA, single-stranded DNA.

© 2008 Mortusewicz et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

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