Question

Gamma radiation of water produces the hydroxyl radical (HO). Write a mechanism showing how hydroxyl radical can ceave and modify DNA.

Answer 1

Hi Answer:

As gamma radiations attack the water molecule it produces the hydroxyl radical (^.OH) or free radical. This free radical damaging of DNA is known as the indirect DNA damage. These hydroxyl radicals are the quintessential reactive oxygen species and it causes much DNA damage as compared to the damage caused by the ionizing radiations.

H₂O⁺ ? H⁺ + OH·

The ·OH radicals damaged the DNA strands by initiating the abstraction of a deoxyribose hydrogen atom. The DNA strands broken by this method is widely used for making footprints of DNA–protein complexes

Mechanism of DNA damage by hydroxyl radicals (·OH) attack

(·OH) radicals attack the DNA backbone and bases and cause a unrepairable damage to the DNA which can be lethal or mutagenic to cells. The (·OH) radicals initiate its reaction by hydrogen abstraction from a deoxyribose carbon which leads to the breakage of DNA strand or release of bases. The reaction order of (^.OH) radicals with the deoxyribose is in the following order 5? H > 4? H > 3? H ? 2? H ? 1? H.

The mechanism of base damage by (·OH) radicals is shown by taking the example of Guanine base. The Guanine base has the lowest reduction potential. (·OH) radical get added at C2-, C4-, C5- and C8-positions of Guanine. Due to the electrophilic nature of (• OH) radical the additions mostly took place at the high electron density sites. The addition reactions generate OH – adduct radicals which have different redox properties. The base damaging process of Guanine is shown in the figure below:

The second proposed mechanism of (^.OH) radicals reaction with DNA bases is the addition of (·OH) radicals at electron- rich, pi bonds. These pi bonds are present between C5-C6 of pyrimidines and N7-C8 in purines bases. When these (·OH) radicals get added to these bonds then there is the formation of several stable products took place, generally, with (·OH) radicals addition, there is the formation of several baseless sites occur due to the beta-elimination which further causes mutation in the DNA strand.