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

Cell Reports (May 2016)

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

Journal volume & issue: Vol. 15, no. 7
pp. 1597 – 1610

Abstract

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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.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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