Radiation Chemistry of D(ApCpGpT)

Abstract

The radiation chemistry of the DNA tetranucleoside triphosphate d(ApCpGpT) was investigated. Irradiations were carried out on aqueous solutions saturated with oxygen (with and without added Cu++), nitrogen or nitrous oxide. When oxygen was present, principal products were formed by hydroxylation at the 8-position of guanine and by degradation of thymine leaving a formamido remnant. Products were also formed containing both of the aforementioned lesions at adjacent deoxyguanosine and pyrimidine nucleosides. Other products resulted from rearrangement of the thymine ring generating two diastereoisomers of the 5-methyl-5-hydroxyhydantoin modification of d(ApCpGpT). Rearrangement of the cytosine ring occurred generating imidazolidine products and a hydantoin product. The product profiles are similar when either an N2O or N2 gaseous environment is maintained. However, in the latter case the dihydrothymine modifications of d(ApCpGpT) are markedly enhanced. Other products include an 8,5' cyclized product formed from the 2'-deoxyadenosine nucleoside and the 8-hydroxyguanine modification. 6-Hydroxy-5,6-dihydrothymine and 5,6-dihydroxy-5,6-dihydrothymine modifications of the thymidine nucleoside were also observed. A strand break product formed in oxygenated solution is also produced in nitrous oxide saturated solutions. Scission of the deoxyadenosine terminus was also observed. The effect of several of these lesions on d(ApCpGpT) as substrate for nuclease P1, bovine spleen phosphodiesterase and snake venom phosphodiesterase was studied.

HO • radicals induce an unexpected high proportion of tandem base lesions refractory to repair by DNA glycosylases

“…Moreover, electron transfer reactions (path C) provide an elegant explanation for the higher yield of 8-oxodGuo formation observed relative to 8-oxodAdo. Through the pioneering work of Box and coworkers (10,12,31,32), the existence of tandem lesions has been described in short oligonucleotides. Here we provide quantitative evidence for the abundance of such lesions in double-stranded DNA exposed to HO…”

Ozone-Induced DNA Damage: A Pandora’s Box of Oxidatively Modified DNA Bases

“…These results contrast those in the literature concerning the digestion of DNA containing N -formamide. Using short oligonucleotides, Box and co-workers reported that P1 nuclease was unable to cleave the phosphodiester bond between N -formamide and nonmodified nucleotide by P1 nuclease, while SVP resulted in cleavage. , In contrast, another study with an array of short and long oligonucleotides reported stalled and partial hydrolysis (40–60%) with P1 nuclease but hardly any hydrolysis with SVP . The reasons for this discrepancy is not clear.…”

Formation of 5′,8-cyclo-2′-deoxyadenosine in single strand DNA. Theoretical quantum mechanics study

“…The cyclization process leads to the creation of a new chiral centre on the C8 carbon atom in the intermediate product. Due to the possibility of adenine rotation around the N-glycosidic bond in 16-18, the following diastereomeric arrangements at C5¢ and C8, in the reaction the following intermediate products are possible: SR( 16), SS (17), RR (18), RS (19) (Fig. 3).…”

“…Chem., 2010, 8, 1603-1609 | 1607 data obtained by g-radiation of aqueous solutions of short ss-DNA (tetramer d[ACGT]). 19 It has been assumed that precursors 6 and 14 of the 5¢R form of 5¢,8-cyclo-2¢-deoxyadenosine-3¢,5¢diphosphate are the most stable ones of the discussed C5¢ radical of 2¢-deoxyadenosine-3¢,5¢-diphosphate in both calculation environments. Moreover, the lowest energetic barrier (7.54/11.3 kcal mol -1 gaseous/aqueous phase) of the 6 → 14 transition would lead to the preferential formation of the 5¢R diastereomeric form in ss-DNA.…”