Published online 8 September 2004
Nucleic Acids Research, Vol. 32 No. 16 © Oxford University Press 2004; all rights reserved
Portrait of transcriptional responses to ultraviolet and ionizing radiation in human cells
Department of Medicine and Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, USA
* To whom correspondence should be addressed at CCSR 1145, Division of Oncology, Stanford University Medical Center, Stanford, CA 94305-5151, USA. Tel: +1 650 725 6442; Fax: +1 650 736 2282; Email: chu{at}cmgm.stanford.edu
Received May 27, 2004; Revised and Accepted August 3, 2004
To understand the human response to DNA damage, we used microarrays to measure transcriptional responses of 10 000 genes to ionizing radiation (IR) and ultraviolet radiation (UV). To identify bona fide responses, we used cell lines from 15 individuals and a rigorous statistical method, Significance Analysis of Microarrays (SAM). By exploring how sample number affects SAM, we rendered a portrait of the human damage response with a degree of accuracy unmatched by previous studies. By showing how SAM can be used to estimate the total number of responsive genes, we discovered that 24% of all genes respond to IR and 32% respond to UV, although most responses were less than 2-fold. Many genes were involved in known damage-response pathways for cell cycling and proliferation, apoptosis, DNA repair or the stress response. However, the majority of genes were involved in unexpected pathways, with functions in signal transduction, RNA binding and editing, protein synthesis and degradation, energy metabolism, metabolism of macromolecular precursors, cell structure and adhesion, vesicle transport, or lysosomal metabolism. Although these functions were not previously associated with the damage response in mammals, many were conserved in yeast. These insights reveal new directions for studying the human response to DNA damage.
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