Sequence specificities in the interactions of chemicals and radiations with DNA

Abstract

Sequence specificities in the interactions of chemicals and radiations with DNA are reviewed. Emphasis is placed on information which has been obtained by adapting DNA sequencing techniques to the detection of DNA damage and modifications. The actions of anti-tumor drugs, non-covalent DNA binders and UV irradiation are discussed in terms of both modifications induced in DNA and the subsequent response of DNA polymerase and repair enzymes. Particular attention is paid to the evidence for 'sequence-specific' interactions of these agents with DNA. It is concluded that while most agents exhibit 'warm' or even 'hot' spots in their interactions with DNA there is not, as yet, compelling evidence for extreme selectivity down to say the gene level in their actions. There does, however, appear to be some affinity, particularly in the case of non-covalent binders, for certain tertiary structures rather than primary sequences per se. In addition, both misincorporation opposite DNA damage and the bypass of damage by polymerases are important phenomena which, to some extent, exhibit sequence specificities. The idea is advanced that DNA structures such as hairpins or cruciforms maybe important in vivo targets for many agents giving rise to specific biological effects.