Human Gene Set: KYNG_ENVIRONMENTAL_STRESS_RESPONSE_DN
Standard name
KYNG_ENVIRONMENTAL_STRESS_RESPONSE_DN
Systematic name
M1776
Brief description
All common down-regulated stress response genes (Human Environmental Stress Response, H-ESR).
Full description or abstract
The accumulation of DNA damage and mutations is considered a major cause of cancer and aging. While it is known that DNA damage can affect changes in gene expression, transcriptional regulation after DNA damage is poorly understood. We characterized the expression of 6912 genes in human primary fibroblasts after exposure to three different kinds of cellular stress that introduces DNA damage: 4-nitroquinoline-1-oxide (4NQO), gamma-irradiation, or UV-irradiation. Each type of stress elicited damage specific gene expression changes of up to 10-fold. A total of 85 genes had similar changes in expression of 3-40-fold after all three kinds of stress. We examined transcription in cells from young and old individuals and from patients with Werner syndrome (WS), a segmental progeroid condition with a high incidence of cancer, and found various age-associated transcriptional changes depending upon the type of cellular stress. Compared to young individuals, both WS and old individuals had similarly aberrant transcriptional responses to gamma- and UV-irradiation, suggesting a role for Werner protein in stress-induced gene expression. Our results suggest that aberrant DNA damage-induced gene regulation may contribute to the aging process and the premature aging in WS.
Collection
C2: Curated CGP: Chemical and Genetic Perturbations
Source publication
Pubmed 15897889 Authors: Kyng KJ,May A,Stevnsner T,Becker KG,Kølvrå S,Bohr VA
