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

Dandliker, Peter J. and Núñez, Megan E. and Barton, Jacqueline K. (1998) Oxidative Charge Transfer To Repair Thymine Dimers and Damage Guanine Bases in DNA Assemblies Containing Tethered Metallointercalators. Biochemistry, 37 (18). pp. 6491-6502. ISSN 0006-2960. doi:10.1021/bi980041w.

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Potent oxidants which intercalate in DNA serve as tools to probe DNA-mediated electron-transfer reactions. A photoexcited rhodium intercalator, Rh(phi)_2DMB^(3+) (phi = 9,10-phenanthrenequinone diimine and DMB = 4,4‘-dimethyl-2,2‘-bipyridine), tethered to DNA, promotes both oxidative damage to 5‘-GG-3‘ doublets in DNA and the repair of thymine dimers from a remote site on the DNA duplex. DNA-mediated repair of a thymine dimer lesion by charge transfer from the tethered rhodium intercalator is quantitative, albeit with low photoefficiency, occurs in an intraduplex reaction over long range (36 Å), and requires that the intervening bases be paired. When both oxidative reactions, repair and oxidative damage, are monitored on the same duplex, competition is evident; the presence of both a 5‘-GG-3‘ site and the thymine dimer diminished the dimer repair efficiency by 20−40% and decreased damage at the 5‘-GG-3‘ sites 2-fold compared to similar sequences lacking either the guanine 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‘-G of the 5‘-GT<>TG-3‘ tetrad only in the presence of thymine dimer. Overall, the yield of repaired thymine strand was at least 10 times higher than the yield of oxidized guanine in the same sequences. While the 5-GG-3‘ may represent the thermodynamically favored site for oxidative reaction, repair of the thymine dimer 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 cannot trigger the repair of the thymine dimer lesion. Oxidative damage to DNA from a distance, mediated by the DNA base pair stack, can, however, be utilized to probe the disruption in the base stack generated by the thymine dimer. The presence of the dimer does not diminish oxidation by a Ru(III) intercalator at a distal guanine doublet, suggesting that the disruption caused by the dimer does not block charge transfer through the DNA duplex. DNA-mediated electron-transfer reactions of metallointercalators therefore serve to illustrate important aspects of radical migration and its consequence with respect to reactions at a distance through the DNA base pair stack.

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Barton, Jacqueline K.0000-0001-9883-1600
Additional Information:© 1998 American Chemical Society. Received January 7, 1998; Revised Manuscript Received March 5, 1998. Publication Date (Web): April 8, 1998. This work was supported by a grant from the NIH (GM49216), as well as by a postdoctoral fellowship to P.J.D. from the Damon Runyon Walter Winchell Cancer Fund and a predoctoral fellowship to M.E.N. from the Howard Hughes Medical Institute. We are grateful to D. Hall, R. E. Holmlin, and E. Stemp for helpful discussions.
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Damon Runyon Walter Winchell Cancer FundUNSPECIFIED
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Issue or Number:18
Record Number:CaltechAUTHORS:20160407-101621786
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Official Citation:Oxidative Charge Transfer To Repair Thymine Dimers and Damage Guanine Bases in DNA Assemblies Containing Tethered Metallointercalators Peter J. Dandliker,‡, Megan E. Núñez, and, and Jacqueline K. Barton Biochemistry 1998 37 (18), 6491-6502 DOI: 10.1021/bi980041w
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:65982
Deposited By: Ruth Sustaita
Deposited On:08 Apr 2016 20:12
Last Modified:10 Nov 2021 23:51

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