DNA and Double-Stranded Oligonucleotides - Free-Radical-Induced DNA Damage and Its Repair - page 411

above-mentioned studies used this approach. These techniques are increasingly
used to follow the rate of hole transfer under well-defined conditions (e.g., Taka-
da et al. 2003a; Yoo et al. 2003; Kawai et al. 2003a).
The reduction potential of 8-oxo-G is only E 7 = 0.74 V/NHE (Steenken et al.
2000) and thus considerably lower than that of G. Consequently, 8-oxo-G acts
as an efficient sink (Doddridge et al. 1998). ET to the radical cation of the sugar
backbone is four times faster from 8-oxo-G than from G (Meggers et al. 2000).
Distant 8-oxo-G may also serve a sink of the hole generated in DNA by the 2-
aminopurine radical cation (Shafirovich et al. 2001) or pyrene radical cation
(Kawai et al. 2001). Trapping of 8-oxo-G • + by water has been suggested to be
faster than 10 5 s − 1 (Kawai et al. 2002). At 77 K, the rate of hole transfer from G • +
to the 8-oxo-G lesion is 7 bp min −1 , and at room temperature this hole transfer

leads to a steady-state of one 8-oxo-G lesion per 127

∼

6 bp, when G • + is generated
in aqueous solution by Br 2 • − (Cai and Sevilla 2003; for the EPR spectrum of 8-
oxo-G • + see Shukla et al. 2004; for the products formed upon oxidation of 8-oxo-
G, see Chap. 10.13). The effects of neighboring Gs on the oxidation of 8-oxo-G
seem to be similar as the oxidation of G in GG pairs (Prat et al. 1998).
For kinetic studies of hole transport, artificial sinks were developed. For ex-
ample, N 2 -cyclopropyldeoxyguanosine efficiently stops hole transport, although
its reduction potential is not much lower (

±

0.13 V) than that of G/C (Nakatani et
al. 2001). Rapid and irreversible cyclopropane ring opening has been suggested
to terminate the hole transport. Similarly, N 6 -cyclopropyldeoxyadenosine inter-
rupts hole transport when placed between two G sites (Dohno et al. 2003). In
contrast, N 2 -phenyldeoxyguanosine suppresses the decomposition of the hole in
its neighborhood (Nakatani et al. 2002a).
Hole transport through genomic DNA has been addressed, and it has been
observed that it is suppressed by BamHI binding (Nakatani et al. 2002b). Mecha-
nistically, this is due to hydrogen bonding of the positively charged guanidine
moiety of BamHI to Gs in its DNA recognition sequence.
The charge transfer through DNA has been shown to play a role in the case
of oxidative thymine cyclobutane dimer repair by a photoexcited tethered rho-
dium intercalator (Dandliker et al. 1997, 1998), in the photoionization of DNA
by 193-nm photons (Melvin et al. 1995a, 1995b, 1998), the oxidation of the modi-
fied base 7-deazaguanine by photoexcited intercalated ethidium bromide (Kel-
ley and Barton 1998). This process slows down considerably when more than
two Ts intervene, and this has been suggested to be due to a proton-coupled ET
(PT-ET) to another species, the neutral radical formed by deprotonation of the
2-aminopurine radical cation (for a theoretical treatment of PT, ET and PT-ET
involving base radical cations, see Llano and Eriksson 2004). Femtosecond spec-
troscopy has been used to study charge transfer from photoexcited 2-aminopu-
rine to DNA that occurs on the picosecond time scale varying strongly with the
neighboring base (10 ps for G and 512 ps for hypoxanthin; Wan et al. 2000).
Using the SO 4 • − radical to form G • + with the help of the pulse radiolysis tech-
nique and tethered pyrene as hole acceptor, it has been shown that the apparent
transfer rates follow the order G • + TG < G • + AC < G • + AG (Takada et al. 2003b).
This means that A is a better medium for hole transfer than T.

∼