DNA and Double-Stranded Oligonucleotides - Free-Radical-Induced DNA Damage and Its Repair - page 409

Table 12 .14. Effective energy of the positive charge (in eV) localized at the middle G in
5 ′ -XGY-3 ′ (X, Y = G, A, C and T) sequences. (Senthilkumar et al. 2003)

Y G A C T

GGY 7.890 8.040 8.310 8.290

AGY 7.900 8.060 8.341 8.320

CGY 7.957 8.115 8.383 8.360

TGY 7.965 8.124 8.407 8.381

Among the nucleobases, G is most readily oxidized (in DNA: + 1.39 V at pH 7;
Milligan et al. 2001a; the corresponding value for Guo has been determined at
+1.29 V; Chap. 10.2). It has been noted (Milligan et al. 2001a) that this differ-
ence is inconsistent with the observation that G groups in polynucleotides are
more easily oxidized than monomeric Gua (Seidel et al. 1996), but this discrep-
ancy is not yet resolved. As mentioned above, GG and GGG sites have even lower
redox potentials. Thus, hot spots in long-range one-electron oxidation of DNA
are GG and GGG sites. There is a marked preference for the 5

′ -G contained in

remote GG and the 5 -and central G in GGG sites (Hall et al. 1996; Stemp et al.

1997; Gasper and Schuster 1997; Saito et al. 1998; Nunez et al. 1999; for calcula-
tions. see Conwell and Basko 2001; Sugiyama and Saito 1996; Senthilkumar et
al. 2003; Saito et al. 1998). The effective energy of the positive charge localized
at the middle G calculated for in 5

′

′ -XGY-3 ′ (X, Y = G, A, C and T) sequences is

given in Table 12.14.
It is seen from this table that a GGG site has the lowest energy, and in GG sites
the base at the 3 ′ -position inf luences the energy much more than the one at the

5 -position. This effect also an important inf luence on which G is oxidized in

a GG site. With a pyrimidine at the 3

′

-G that is oxi-
dized. These calculations are met by experimental data (Hall et al. 1996; Ito et al.
1993; O'Neill et al. 2001; Melvin et al. 1995b; Sanii and Schuster 2000; Nakatani
et al. 1999; Ito and Kawanishi 1997). At GGG sites, it is largely the G in the middle
that is oxidized. An oxidation of the 5

′ -position, it is largely the 5 ′

-A (Senthilkumar et
al. 2003). Again, this conclusion is met by experiments (Hall et al. 1996; Ito et al.
1993; Ito and Kawanishi 1997; Yoshioka et al. 1999). The forward rate from G • +
to a GG site through one interlaced A has been determined at

′ -G is facilitated by a 5 ′

10 7 s − 1 and the

∼ 5 ×

10 6 s −1 (Lewis et al. 2000b).
Base pairing (hydrogen bonding) of G with C reduces the reduction potential
of G with respect of unpaired G (Kawai et al. 2000b). Substituting C by 5-MeC in
DNA may reduce the oxidation potential of the opposing G as compared to the
normal GC pair, and one might expect that such a site is capable of trapping the
hole more effectively, but no effect was detectable (Kanvah and Schuster 2004).

reverse rate at 5 ×