Journal
CELL CYCLE
Volume 6, Issue 8, Pages 972-981Publisher
TAYLOR & FRANCIS INC
DOI: 10.4161/cc.6.8.4106
Keywords
microarray; cell cycle; ionizing radiation; human fibroblasts; EPIG
Categories
Funding
- Intramural NIH HHS [Z99 ES999999] Funding Source: Medline
- NIEHS NIH HHS [P30 ES010126, ES10126, U19 ES011391, N01ES25497, ES11391] Funding Source: Medline
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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.
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