Cellular Stress Responses to DNA Damage: An Intracellular Balance between Life, Senescence, and Death

A. A. Rommel, E. Goetz, M. Suzuki, S. Araki, J. Morales, Y. Zou, X. Luo, D. A. Boothman, K. S. Leskov, S. Matsuyama, M. W. Jackson, G. Veneziano, L. D. Mayo

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Recent cellular and molecular biological examination of DNA repair, cell cycle checkpoints, apoptosis, differentiation, and stress-induced premature senescence (SIPS) in response to genotoxic stress is largely responsible for the current understanding of the interplay between cell stress responses and human diseases, such as cancer. Human pathologies associated with older individuals show homeostatic alterations of several cell stress factors, including Bax, p53, Hdm2, and secretory clusterin (sCLU) that can influence survival, senescence, and ultimately the risk of cancer. Understanding cell stress responses in the context of genetic predispositions is vital to the understanding of cancer risk from environmental stress, such as exposure to low doses of ionizing radiation (IR). Increased expression of sCLU appears to be a sensitive marker of exposure. Its interplay and regulation with stress-induced alterations in Bax, Ku70, Hdm2, p53, and their roles in regulation of survival and carcinogenesis are discussed. Understanding the mechanisms of induction and repression of the cellular responses to genotoxic agents is essential for understanding downstream cancer initiation and progression.

Original languageEnglish (US)
Title of host publicationEncyclopedia of Environmental Health
PublisherElsevier Inc.
Pages543-552
Number of pages10
ISBN (Print)9780444522726
DOIs
StatePublished - Jan 1 2011

Keywords

  • AKT
  • Apoptosis
  • Bax
  • Hdm2
  • IGF-1
  • Ionizing radiation
  • Ku70
  • P53
  • SCLU
  • Senescence
  • Transforming growth factor β1 (TGF-β1)

ASJC Scopus subject areas

  • General Environmental Science

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