Cell Death in Response to Genotoxic Stress and DNA Damage

doi:10.1017/CBO9780511976094.008

8 - Cell Death in Response to Genotoxic Stress and DNA Damage

from Part I - General Principles of Cell Death

Published online by Cambridge University Press: 07 September 2011

Douglas R. Green

Pablo Lopez-Bergami and

Ze'ev Ronai

Edited by

John C. Reed

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Douglas R. Green: Affiliation:
St. Jude Children's Research Hospital, Memphis, Tennessee
Pablo Lopez-Bergami: Affiliation:
Instituto de Biologia y Medicina Experimental
Ze'ev Ronai: Affiliation:
Sanford-Burnham Medical Research Institute
John C. Reed: Affiliation:
Sanford-Burnham Medical Research Institute, La Jolla, California

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Summary

Cells are subjected to multiple types of stress throughout their life cycle, including starvation, infection, and physical and chemical agents. Stressors cause transient and permanent damage. Transient damage is reflected at the level of the protein or RNA and is largely associated with the generation of reactive oxygen radicals, which directly or indirectly impact translation, folding, or conformation of proteins. In contrast to transient damage, which is expected to be cleared by existing cellular machinery that allows recognition and removal of damaged proteins, permanent damage is primarily reflected at the level of the DNA, although it could also result from damaged proteins that fail to support proper repair or cell duplication. DNA-damaging agents induce a variety of modifications that may result in improper chromosomal duplication, recombination between chromosomes, gene mutations, or gene amplification, which may result in malignant transformations if not properly repaired. Damage is generated by both endogenous and exogenous sources: endogenous (spontaneous) damage is caused by agents within the cell itself (i.e., the products of normal cellular metabolism, replication, mitosis), whereas exogenous sources include ultraviolet (UV) light, ionizing radiation (IR), and environmental genotoxins (e.g., alkylating compounds, polycyclic aromatic hydrocarbons, biphenyls, and heterocyclic amines). Most cytotoxic anticancer drugs react either directly or indirectly (through reactive metabolites) with DNA or by blocking DNA-metabolizing functions, such as DNA polymerases or topoisomerases.

Type: Chapter
Information: Apoptosis
Physiology and Pathology
, pp. 74 - 87

DOI: https://doi.org/10.1017/CBO9780511976094.008 [Opens in a new window]

Publisher: Cambridge University Press

Print publication year: 2011

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