DNA and Double-Stranded Oligonucleotides - Free-Radical-Induced DNA Damage and Its Repair - page 386

DNA protein cross-links are quite abundant DNA lesions in mammalian cells,

but per se they are not lethal and can be enzymatically repaired (Chiu et al. 1989,
1990; Oleinick et al. 1986; Chiou et al. 1984).

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12 .7
5-Halouracil-Substituted DNA

5-Bromo- or 5-iodouracil-substituted DNA has been investigated in some de-
tail for studying free-radical-induced strand breakage (ALSs; for reviews see
Hutchinson and Köhnlein 1980; Hutchinson 1987). Moreover, BudR-labeling
CHO cells induces quite significantly sister chromatid exchanges (SCE) upon
treatment with UV and ionizing radiation (Wojcik et al. 1999, 2003; Bruck-
mann et al. 1999). The 5-uracilyl radical formed by either photolysis or ion-
izing radiation is capable of abstracting a hydrogen from a neighboring sugar
moiety (Chap. 10.7). This leads to an ALS and subsequently to an SSB (Krasin
and Hutchinson 1978a; Hewitt and Marburger 1975), but DSBs are also ob-
served in a single photochemical event in BudR-labeled E. coli cells (Krasin
and Hutchinson 1978b). This is one of the many indications that in dsODNs
and in DNA the photochemical reaction is much more complex than in the
simple model systems that were described in Chapter 10.7. The quantum yield
of Ura formation of 5BrUra in dilute aqueous solution in the presence of low
concentrations of H-donors is more than an order of magnitude lower than
that of SSB formation in 5BrUra-substituted DNA (Campbell et al. 1974). This
has been attributed to a prevention of cage recombination by scavenging caged
radicals. However, there is a strong inf luence of neighboring bases (Murray
and Martin 1989), and this is not compatible with a simple homolytic cleavage
of the C Hal bond as in the photolysis of the halouracils without such neigh-

boring effects.
From an extended study on the sequence selectivity of UV-induced cleavage
of dsODNs (Table 12.12) it has been concluded that an ET to neighboring bases
must occur [reaction (40)] followed by a subsequent competition between elec-
tron backdonation [reaction (41)], decay of the 5BrUra radical anion [reaction
(42)] and hole transfer [reaction (43); Chen et al. 2000.

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