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DNA Damage Response and the Balance Between Cell Survival and Cell Death

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Part of the Cancer Drug Discovery and Development book series (CDD&D)

Abstract

DNA damage induces the activation of a cascade of kinases that trigger the DNA damage response (DDR). Downstream are targets that either help cells to survive or undergo cell death. DNA damage-induced cell death is executed by apoptosis, necrosis, mitotic catastrophe, and autophagy. Of these different forms of cell inactivation, apoptosis is often the main route of cell death following DNA damage. Cells undergo apoptosis upon genotoxic stress via the death receptor and/or the intrinsic mitochondrial damage pathway, with p53 and AP-1 involved decisively. Not every type of DNA damage induces apoptosis. Many DNA lesions are tolerated by the cell, some are mutagenic without being toxic and some are more toxic than mutagenic. Severe DNA damages are O6-alkylguanines, bulky lesions, and DNA double-strand breaks, that activate DDR and downstream survival and death signals. The survival and death pathways triggered by upstream DDR functions will be discussed in this chapter.

Keywords

Checkpoints Cell cycle DNA damage response DNA repair p53 Apoptosis Death receptors Fas ATM ATR Anticancer drugs 

Notes

Acknowledgements:

This work of the authors is supported by Deutsche Forschungsgemeinschaft, Mildred-Scheel Stiftung für Krebsforschung und Stiftung Rheinland-Pfalz.

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© Humana Press, a part of Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of ToxicologyUniversity of MainzMainzGermany

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