Upon incorporation into cellular DNA, halogenated nucleosides 5-bromo-2'-deoxyuridine (BrdU) and 5-iodo-2'-deoxyuridine (IdU) are well known to sensitize cells to UV irradiation. We report here for the first time that the efficiency of UVB- and UVA-induced dehalogenation of these nucleotides are strand-type independent.  Upon UVA exposure, IdU generated 50% more dU than BrdU, which reflects the fact that IdU absorbs better in the UVA range.  With UVB light, the opposite trend was observed.  UV irradiation also yielded the d(G[8-5]U) intrastrand crosslink, which was induced at the highest frequency with UVB light in double-stranded IdU-bearing ODNs. Density functional theory calculations (B3LYP/LANL2DZdp) confirmed that the dissociative electron attachment reaction is much more favorable with IdU- than BrdU-containing ODN.   Our findings support mechanistic studies suggesting that crosslink products are formed via electron transfer and heterolytic cleavage of the C5-X bond, whereas dU results from homolytic cleavage of the C5-X bond and subsequent hydrogen abstraction.

Comparative biological and DTF study of the formation of intrastrand crosslink and dehalogenation products from the UVB and UVA irradiation of single- and double-stranded DNA containing a 5-iodo-2'-deoxyuridine and 5-bromo-2'-deoxyuridine

243rd National Meeting (2012)

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