Oxidative Charge Transfer To Repair Thymine Dimers and Damage Guanine Bases in DNA Assemblies Containing Tethered Metallointercalators

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• 作者：Peter J. Dandliker ; Megan E. Nú ; ñ ; ez ; and Jacqueline K. Barton
• 刊名：Biochemistry
• 出版年：1998
• 出版时间：May 5, 1998
• 年：1998
• 卷：37
• 期：18
• 页码：6491 - 6502
• 全文大小：274K
• 年卷期：v.37,no.18(May 5, 1998)
• ISSN：1520-4995

文摘

Potent oxidants which intercalate in DNA serve as tools to probeDNA-mediated electron-transfer reactions. A photoexcited rhodium intercalator,Rh(phi)₂DMB³⁺ (phi =9,10-phenanthrenequinonediimine and DMB = 4,4'-dimethyl-2,2'-bipyridine), tethered to DNA,promotes both oxidative damageto 5'-GG-3' doublets in DNA and the repair of thymine dimers from aremote site on the DNA duplex.DNA-mediated repair of a thymine dimer lesion by charge transferfrom the tethered rhodium intercalatoris quantitative, albeit with low photoefficiency, occurs in anintraduplex reaction over long range (36 Å),and requires that the intervening bases be paired. When bothoxidative reactions, repair and oxidativedamage, are monitored on the same duplex, competition is evident; thepresence of both a 5'-GG-3' siteand the thymine dimer diminished the dimer repair efficiency by20-40% and decreased damage at the5'-GG-3' sites 2-fold compared to similar sequences lacking either theguanine doublet or thymine dimer,respectively. In addition to damage at the 5'-G of 5'-GG-3' sites,we also observe oxidation at the 3'-Gof the 5'-GT<>TG-3' tetrad only in the presence of thymine dimer.Overall, the yield of repaired thyminestrand was at least 10 times higher than the yield of oxidized guaninein the same sequences. While the5-GG-3' may represent the thermodynamically favored site for oxidativereaction, repair of the thyminedimer appears to be kinetically more favorable. Dipyridophenanzine(dppz) complexes of ruthenium(III), less potent oxidants which intercalate in DNA, oxidize 5'-GG-3'doublets efficiently but cannottrigger the repair of the thymine dimer lesion. Oxidative damageto DNA from a distance, mediated bythe DNA base pair stack, can, however, be utilized to probe thedisruption in the base stack generated bythe thymine dimer. The presence of the dimer does not diminishoxidation by a Ru(III) intercalator at adistal guanine doublet, suggesting that the disruption caused by thedimer does not block charge transferthrough the DNA duplex. DNA-mediated electron-transfer reactionsof metallointercalators thereforeserve to illustrate important aspects of radical migration and itsconsequence with respect to reactions ata distance through the DNA base pair stack.