DNA damage responses to oxidative stress

The DNA damage response is a hierarchical process. DNA damage is detected by sensor proteins such as the MRN complex that transmit the information to transducer proteins such as ATM and ATR, which control the damage response through the phosphorylation of effector proteins. The extent of the DNA dam...

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Bibliographic Details
Published in:DNA Repair 2004-08, Vol.3 (8), p.1109-1115
Main Authors: Barzilai, Ari, Yamamoto, Ken-Ichi
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Cell Cycle
Cell Lineage
Damage
DNA
DNA Damage
DNA Repair
Humans
Hypoxia
Mitochondria - pathology
Oxidation-Reduction
Oxidative Stress
Reactive Oxygen Species
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Summary:The DNA damage response is a hierarchical process. DNA damage is detected by sensor proteins such as the MRN complex that transmit the information to transducer proteins such as ATM and ATR, which control the damage response through the phosphorylation of effector proteins. The extent of the DNA damage determines cell fate: cell cycle arrest and DNA repair or the activation of apoptotic pathways. In aerobic cells, reactive oxygen species (ROS) are generated as a by-product of normal mitochondrial activity. If not properly controlled, ROS can cause severe damage to cellular macromolecules, especially the DNA. We describe here some of the cellular responses to alterations in the cellular redox state during hypoxia or oxidative stress. Oxidative damage in DNA is repaired primarily via the base excision repair (BER) pathway which appears to be the simplest of the three excision repair pathways. To allow time for DNA repair, the cells activate their cell cycle checkpoints, leading to cell cycle arrest and preventing the replication of damage and defective DNA.
ISSN:1568-7864
1568-7856
DOI:10.1016/j.dnarep.2004.03.002