Protection of DNA Against Free-Radical Attack

With thiols, protection against free-radical attack and repair of DNA damage (Sect. 12.12) is not always easy to disentangle in in vitro experiments and even more so in cellular systems (e.g., Murray et al. 1990). This has to be kept in mind, when some aspects of thiol protections are discussed here. 

As in the case of poly(U), which has been studied as a model system in some detail (Chap. 11.2), there is a relationship of the rate of protection of DNA by thiols and disulfides and the charge of the sulfur compound due to ion condensation (for evidence of this phenomenon, see Smoluk et al. 1988b). As has been measured by following the protection of DNA irradiated in aqueous solution against base release (Zheng et al. 1988), G(base release) follows the equation G0/Gp = 1 + 3[RSH]. The data, compiled in Table 12.16, have been interpreted in terms of electrostatic interaction of thiols of the thiols/disulfides with DNA leading to higher concentrations of cations with respect to neutral thiols/disulfides 

The effective charge Z of the disulfide derived from WR 1065, WR 33274, is near +4 and hence accumulates even more strongly near the DNA accounting for very effective OH scavenging. In addition, it protects DNA by compaction (Savoye et al. 1997). It is not homogeneously distributed along the DNA double helix. As a consequence, there are hot spots of protected and unprotected regions. 

In all of these reactions, thiyl radicals are formed which are still quite reactive in many aspects (Chap. 7.4). In a cellular environment, they will have to be inactivated. Originally, 02 was thought to be the radical sink according to reactions (78) and (79), but more recent kinetic evidence has shown that it may be the ascorbate radical [reaction (80)] (Wardman 1995, 1998). 

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