title: A UV-induced genetic network links the RSC complex to nucleotide excision repair and shows dose-dependent rewiring.
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.
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, CA 92037, USA.
authors.forename: Rohith
authors.initials: R
authors.lastname: Srivas
authors.affiliation: Department of Toxicogenetics, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, the Netherlands.
authors.forename: Thomas
authors.initials: T
authors.lastname: Costelloe
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, CA 92037, USA.
authors.forename: Anne-Ruxandra
authors.initials: AR
authors.lastname: Carvunis
authors.affiliation: Department of Oncology, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK.
authors.forename: Sovan
authors.initials: S
authors.lastname: Sarkar
authors.affiliation: Department of Toxicogenetics, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, the Netherlands.
authors.forename: Erik
authors.initials: E
authors.lastname: Malta
authors.affiliation: Department of Toxicogenetics, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, the Netherlands.
authors.forename: Su Ming
authors.initials: SM
authors.lastname: Sun
authors.affiliation: Department of Toxicogenetics, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, the Netherlands.
authors.forename: Marijke
authors.initials: M
authors.lastname: Pool
authors.affiliation: Department 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.
authors.forename: Katherine
authors.initials: K
authors.lastname: Licon
authors.affiliation: Division of Gene Regulation, Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands.
authors.forename: Tibor
authors.initials: T
authors.lastname: van Welsem
authors.affiliation: Division of Gene Regulation, Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands.
authors.forename: Fred
authors.initials: F
authors.lastname: van Leeuwen
authors.affiliation: Department of Oncology, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: McHugh
authors.affiliation: Department of Toxicogenetics, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, the Netherlands. Electronic address: h.van.attikum@lumc.nl.
authors.forename: Haico
authors.initials: H
authors.lastname: van Attikum
authors.affiliation: Department 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.
authors.forename: Trey
authors.initials: T
authors.lastname: Ideker
mesh_terms: D042002:Chromatin Assembly and Disassembly; D004260:DNA Repair; D004307:Dose-Response Relationship, Radiation; D053263:Gene Regulatory Networks / Q000528:radiation effects*; D016681:Genome, Fungal; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism / Q000528:radiation effects; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D029701:Saccharomyces cerevisiae Proteins