Question

In a few sentences explain how reactive oxygen species can cause damage to DNA

Answer 1

1. Reactive oxygen species (ROS) are chemically reactive molecules containing oxygen. The hydroxyl radical is extremely reactive that immediately removes electrons from any molecule in its path, turning that molecule into a free radical and so propagating a chain reaction.

2. However, hydrogen peroxide is actually more damaging to DNA than the hydroxyl radical, since the lower reactivity of hydrogen peroxide provides enough time for the molecule to travel into the nucleus of the cell, subsequently wreaking havoc on macromolecules such as DNA.

3. ROS are a major source of DNA damage. ROS can cause oxidative damages to nuclear, mitochondrial, and chloroplastic DNA. DNA is cell’s genetic material and any damage to the DNA can result in changes in the encoded proteins, which may lead to malfunctions or complete inactivation of the encoded proteins.

4. Oxidative attack on DNA results in deoxyribose oxidation, strand breakage, removal of nucleotides, variety of modifications in the organic bases of the nucleotides, and DNA-protein crosslinks. Further, changes in the nucleotides of one strand can result in the mismatches with the nucleotides in the other strand, yielding subsequent mutations.

5. Enhanced DNA degradation has been observed in plants exposed to various environmental stresses such as salinity and metal toxicity. Both the sugar and base moieties of DNA are susceptible to oxidation by ROS. Oxidative attack to DNA bases generally involves •OH addition to double bonds, while sugar damage mainly results from hydrogen abstraction from deoxyribose.

6. The hydroxyl radical is known to react with all purine and pyrimidine bases and, also, the deoxyribose backbone [105]. •OH generates various products from the DNA bases which mainly include C-8 hydroxylation of guanine to form 8-oxo-7,8 dehydro-2′- deoxyguanosine, hydroxymethyl urea, urea, thymine glycol, thymine and adenine ring-opened, and saturated products.

7. 8-Hydroxyguanine is the most commonly observed product. 1O2 only reacts with guanine, whereas H₂O₂ and O₂•− do not react with bases. ROS-induced DNA damages include various mutagenic alterations as well. For example, mutation arising from selective modification of G:C sites, especially, indicates oxidative attack on DNA by ROS. ROS attack DNA bases indirectly through reactive products generated by ROS attack to other macromolecules such as lipid.

8. ROS attack to DNA sugars leads to single-strand breaks. ROS abstract hydrogen atom from the C4 position of deoxyribose, leading to generation of a deoxyribose radical that further reacts to produce DNA strand breakage . 9. Under physiological conditions, neither H₂O₂ alone nor O2•− can cause in vitro strand breakage. Therefore, it was concluded that the toxicity associated with these ROS in vivo is most likely the result of Fenton reaction. When •OH attacks on either DNA or proteins associated with it, DNA protein crosslinks are formed .

10. DNA protein crosslinks cannot be readily repaired and may be lethal if replication or transcription precedes repair. Mitochondrial and chloroplast DNA are more susceptible to oxidative damage than nuclear DNA due to the lack of protective protein, histones, and close locations to the ROS producing systems in the former. Even though repair system exists for damaged DNA, excessive changes caused by ROS lead to permanent damage to the DNA with potentially detrimental effects for the cell.