Book of Abstracts: Albany 2007
June 19-23 2007
Structures and Mechanisms of DNA Damage Mediated by Transition Metals
The heterocyclic bases of DNA are both sensitive to oxidation as well as excellent sites for interaction with transition metal complexes. Depending upon the mechanism, unusual oxidized structures are generated presenting challenges for DNA replication and repair. Metal complexes that act as one-electron oxidants lead to guanine oxidation forming initially either 8-oxoguanosine or an imidazolone product. 8-Oxoguanosine is subject to further oxidation providing hydantoins as final products. Metal complexes that involve electron transfer with superoxide formation can leapfrog 8-oxoG formation giving hydantoins directly. The hydantoin lesions guanidinohydantoin and spiroiminodihydantoin have been detected in repair-deficient E. coli subjected to chromate. Mutagenesis assays indicate that the hydantoins are highly mutagenic leading to G to C and G to T transversion mutations. Current hypotheses and structural investigations suggest that hydantoins may be read as Watson-Crick T mimics (accounting for A insertion opposite the lesion) or as a mimic of T in a T:G wobble pair.
Cynthia J. Burrows*
Department of Chemistry