Repair of exocyclic DNA adducts: rings of complexity

Exocyclic DNA adducts are mutagenic lesions that can be formed by both exogenous and endogenous mutagens/carcinogens. These adducts are structurally analogs but can differ in certain features such as ring size, conjugation, planarity and substitution. Although the information on the biological role of the repair activities for these adducts is largely unknown, considerable progress has been made on their reaction mechanisms, substrate specificities and kinetic properties that are affected by adduct structures. At least four different mechanisms appear to have evolved for the removal of specific exocyclic adducts. These include base excision repair, nucleotide excision repair, mismatch repair, and AP endonuclease-mediated repair. This overview highlights the recent progress in such areas with emphasis on structure-activity relationships. It is also apparent that more information is needed for a better understanding of the biological and structural implications of exocyclic adducts and their repair.