Nucleic acid sequence and repair: role of adduct, neighbor bases and enzyme specificity

The study of the role of sequence in base modification was mainly started in the 1980s in terms of sequence selectivity for mutational events (see for example 1–20). These events were generally roduced by environmental agents, such as UV exposure, alkylating agents and aromatic amines, or spontaneously ( 21 ). It has since become clear that such events are not totally random but tend to predominate at specific sites in nucleic acids. This type of investigation led to the idea of `targeted' mutation, which was often related to specific cellular changes in function. At the onset of the interest in how base sequence affected modification, there was also interest in whether the base sequences flanking damage could also influence replication (see for example 22–25) and repair (see for example 7,8,13,26–28). Significant progress in these research areas was accelerated when it became feasible to design and construct synthetic oligonucleotides with site-directed modified bases ( 29 ). In addition, it became generally accepted that nucleic acid sequence and structure are closely linked. Changes in both primary and secondary structures resulting from neighboring bases were presumed to be one of the important factors affecting replication and repair, both qualitatively and quantitatively.