Multiomic Analysis of the UV-Induced DNA Damage Response
Stefan Boeing,
Laura Williamson,
Vesela Encheva,
Ilaria Gori,
Rebecca E. Saunders,
Rachael Instrell,
Ozan Aygün,
Marta Rodriguez-Martinez,
Juston C. Weems,
Gavin P. Kelly,
Joan W. Conaway,
Ronald C. Conaway,
Aengus Stewart,
Michael Howell,
Ambrosius P. Snijders,
Jesper Q. Svejstrup
Affiliations
Stefan Boeing
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
Laura Williamson
Mechanisms of Transcription Laboratory, the Francis Crick Institute, Clare Hall Laboratories, South Mimms EN6 3LD, UK
Vesela Encheva
Protein Analysis and Proteomics Laboratory, the Francis Crick Institute, Clare Hall Laboratories, South Mimms EN6 3LD, UK
Ilaria Gori
High Throughput Screening Laboratory, the Francis Crick Institute, 44 Lincoln’s Inn Fields, London WC2A 3LY, UK
Rebecca E. Saunders
High Throughput Screening Laboratory, the Francis Crick Institute, 44 Lincoln’s Inn Fields, London WC2A 3LY, UK
Rachael Instrell
High Throughput Screening Laboratory, the Francis Crick Institute, 44 Lincoln’s Inn Fields, London WC2A 3LY, UK
Ozan Aygün
Mechanisms of Transcription Laboratory, the Francis Crick Institute, Clare Hall Laboratories, South Mimms EN6 3LD, UK
Marta Rodriguez-Martinez
Mechanisms of Transcription Laboratory, the Francis Crick Institute, Clare Hall Laboratories, South Mimms EN6 3LD, UK
Juston C. Weems
Stowers Institute for Medical Research, Kansas City, MO 64110, USA
Gavin P. Kelly
Bioinformatics and Biostatistics Laboratory, the Francis Crick Institute, 44 Lincoln’s Inn Fields, London WC2A 3LY, UK
Joan W. Conaway
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
Ronald C. Conaway
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
Aengus Stewart
Bioinformatics and Biostatistics Laboratory, the Francis Crick Institute, 44 Lincoln’s Inn Fields, London WC2A 3LY, UK
Michael Howell
High Throughput Screening Laboratory, the Francis Crick Institute, 44 Lincoln’s Inn Fields, London WC2A 3LY, UK
Ambrosius P. Snijders
Protein Analysis and Proteomics Laboratory, the Francis Crick Institute, Clare Hall Laboratories, South Mimms EN6 3LD, UK
Jesper Q. Svejstrup
Mechanisms of Transcription Laboratory, the Francis Crick Institute, Clare Hall Laboratories, South Mimms EN6 3LD, UK; Corresponding author
Summary: 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. : Boeing et al. investigate the UV-induced DNA damage response by combining a range of proteomic and genomic screens. A function in this response for the melanoma driver STK19 as well as a number of other factors are uncovered.
