title: Multiomic Analysis of the UV-Induced DNA Damage Response.
abstract: In order to facilitate the identification of factors and pathways in the cellular response to UV-induced DNA damage, several descriptive proteomic screens and a functional genomics screen were performed in parallel. Numerous factors could be identified with high confidence when the screen results were superimposed and interpreted together, incorporating biological knowledge. A searchable database, bioLOGIC, which provides access to relevant information about a protein or process of interest, was established to host the results and facilitate data mining. Besides uncovering roles in the DNA damage response for numerous proteins and complexes, including Integrator, Cohesin, PHF3, ASC-1, SCAF4, SCAF8, and SCAF11, we uncovered a role for the poorly studied, melanoma-associated serine/threonine kinase 19 (STK19). Besides effectively uncovering relevant factors, the multiomic approach also provides a systems-wide overview of the diverse cellular processes connected to the transcription-related DNA damage response.
authors.affiliation: Mechanisms of Transcription Laboratory, the Francis Crick Institute, Clare Hall Laboratories, South Mimms EN6 3LD, UK; Bioinformatics and Biostatistics Laboratory, the Francis Crick Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
authors.forename: Stefan
authors.initials: S
authors.lastname: Boeing
authors.affiliation: Mechanisms of Transcription Laboratory, the Francis Crick Institute, Clare Hall Laboratories, South Mimms EN6 3LD, UK.
authors.forename: Laura
authors.initials: L
authors.lastname: Williamson
authors.affiliation: Protein Analysis and Proteomics Laboratory, the Francis Crick Institute, Clare Hall Laboratories, South Mimms EN6 3LD, UK.
authors.forename: Vesela
authors.initials: V
authors.lastname: Encheva
authors.affiliation: High Throughput Screening Laboratory, the Francis Crick Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Gori
authors.affiliation: High Throughput Screening Laboratory, the Francis Crick Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: Saunders
authors.affiliation: High Throughput Screening Laboratory, the Francis Crick Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
authors.forename: Rachael
authors.initials: R
authors.lastname: Instrell
authors.affiliation: Mechanisms of Transcription Laboratory, the Francis Crick Institute, Clare Hall Laboratories, South Mimms EN6 3LD, UK.
authors.forename: Ozan
authors.initials: O
authors.lastname: Aygün
authors.affiliation: Mechanisms of Transcription Laboratory, the Francis Crick Institute, Clare Hall Laboratories, South Mimms EN6 3LD, UK.
authors.forename: Marta
authors.initials: M
authors.lastname: Rodriguez-Martinez
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
authors.forename: Juston C
authors.initials: JC
authors.lastname: Weems
authors.affiliation: Bioinformatics and Biostatistics Laboratory, the Francis Crick Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
authors.forename: Gavin P
authors.initials: GP
authors.lastname: Kelly
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO 64110, USA; Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors.forename: Joan W
authors.initials: JW
authors.lastname: Conaway
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO 64110, USA; Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Conaway
authors.affiliation: Bioinformatics and Biostatistics Laboratory, the Francis Crick Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
authors.forename: Aengus
authors.initials: A
authors.lastname: Stewart
authors.affiliation: High Throughput Screening Laboratory, the Francis Crick Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Howell
authors.affiliation: Protein Analysis and Proteomics Laboratory, the Francis Crick Institute, Clare Hall Laboratories, South Mimms EN6 3LD, UK.
authors.forename: Ambrosius P
authors.initials: AP
authors.lastname: Snijders
authors.affiliation: Mechanisms of Transcription Laboratory, the Francis Crick Institute, Clare Hall Laboratories, South Mimms EN6 3LD, UK. Electronic address: jesper.svejstrup@crick.ac.uk.
authors.forename: Jesper Q
authors.initials: JQ
authors.lastname: Svejstrup
mesh_terms: D002843:Chromatin / Q000378:metabolism; D004249:DNA Damage / Q000528:radiation effects*; D016208:Databases, Factual; D057809:HEK293 Cells; D006801:Humans; D020407:Internet; D007976:Leupeptins / Q000494:pharmacology; D053858:Metabolic Networks and Pathways / Q000187:drug effects / Q000528:radiation effects; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation / Q000528:radiation effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D020543:Proteome / Q000187:drug effects / Q000528:radiation effects; D040901:Proteomics; D012319:RNA Polymerase II / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D014158:Transcription, Genetic / Q000528:radiation effects; D054875:Ubiquitination / Q000528:radiation effects; D014466:Ultraviolet Rays; D014584:User-Computer Interface
chemical_list: D002843:Chromatin; D007976:Leupeptins; D009687:Nuclear Proteins; D020543:Proteome; D034741:RNA, Small Interfering; D017346:Protein Serine-Threonine Kinases; C087996:STK19 protein, human; D012319:RNA Polymerase II; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde