Identification of Primary Transcriptional Regulation of Cell Cycle-Regulated Genes upon DNA Damage

 Abstract

The changes in global gene expression in response to DNA damage may derive from either direct induction or repression by transcriptional regulation or indirectly by synchronization of cells to specific cell cycle phases, such as G1 or G2. We developed a model that successfully estimated the expression levels of >400 cell-cycle-regulated genes in normal human fibroblasts based on the proportions of cells in each phase of the cell cycle. By isolating effects on the gene expression associated with the cell cycle phase redistribution after genotoxin treatment, the direct transcriptional target genes were distinguished from genes for which expression changed secondary to cell synchronization. Application of this model to ionizing radiation (IR)-treated normal human fibroblasts identified 150 of 406 cycle-regulated genes as putative direct transcriptional targets of IR-induced DNA damage. Changes in expression of these genes after IR treatment derived from both direct transcriptional regulation and cell cycle synchronization.

Full Text Options
Article
Metrics
 Share
 Info
Pages
972 - 981
doi
10.4161/cc.6.8.4106
Type
Report
 Metrics
 Cite This Article
 Permissions
 Permissions
 Reprints
Identification of Primary Transcriptional Regulation of Cell Cycle-Regulated Genes upon DNA Damage