Figure 3 Sensitivity of DNA-mediated long-range chemical reactions to base stacking. (A) The long-range oxidation of distal guanine doublets is decreased in the presence of intervening bulges disrupting base stacking [18]. (B) Long-range repair of thymine dimers is attenuated in the presence of bulges [22].

Thymine dimers are mutagenic photoproducts formed at contiguous thymines. In bacterial systems they are repaired by reductive electron transfer in a reaction catalyzed by DNA photolyase [5]. Molecular photooxidants can also repair these lesions, and can do so from remote positions within DNA assemblies. Long-range, oxidative repair of thymine dimers was investigated in synthetic DNA duplexes containing a thymine dimer positioned systematically along the helix and a photooxidant, Rh(phi)2bpy3+, tethered to one of the termini [22]. Following irradiation of the modified duplex, the extent of T<>T repair was detected by HPLC. These experiments showed that significant amounts of T<>T repair occurred over distances of as much as 25 Å. The ability of the DNA helix to

mediate this reaction is contingent on a fully stacked pathway, as the introduction of bulged regions into the intervening bases diminished reactivity (Figure 3B).