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Cell Rep. 2013 Dec 26;5(6):1714-24. doi: 10.1016/j.celrep.2013.11.035. Epub 2013 Dec 19.

A UV-induced genetic network links the RSC complex to nucleotide excision repair and shows dose-dependent rewiring.

Author information

  • 1Department of Medicine, University of California, San Diego, La Jolla, CA 92037, USA.
  • 2Department of Toxicogenetics, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, the Netherlands.
  • 3Department of Oncology, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK.
  • 4Department of Medicine, University of California, San Diego, La Jolla, CA 92037, USA; Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92037, USA.
  • 5Division of Gene Regulation, Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands.
  • 6Department of Toxicogenetics, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, the Netherlands. Electronic address: h.van.attikum@lumc.nl.
  • 7Department of Medicine, University of California, San Diego, La Jolla, CA 92037, USA; Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92037, USA. Electronic address: tideker@ucsd.edu.

Abstract

Efficient repair of UV-induced DNA damage requires the precise coordination of nucleotide excision repair (NER) with numerous other biological processes. To map this crosstalk, we generated a differential genetic interaction map centered on quantitative growth measurements of >45,000 double mutants before and after different doses of UV radiation. Integration of genetic data with physical interaction networks identified a global map of 89 UV-induced functional interactions among 62 protein complexes, including a number of links between the RSC complex and several NER factors. We show that RSC is recruited to both silenced and transcribed loci following UV damage where it facilitates efficient repair by promoting nucleosome remodeling. Finally, a comparison of the response to high versus low levels of UV shows that the degree of genetic rewiring correlates with dose of UV and reveals a network of dose-specific interactions. This study makes available a large resource of UV-induced interactions, and it illustrates a methodology for identifying dose-dependent interactions based on quantitative shifts in genetic networks.

Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

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