Interstrand psoralen cross-links do not introduce appreciable bends in DNA

Analysis of the X-ray crystallographic structure of an 8-methoxypsoralen-thymine monoadduct has led to the suggestion that psoralen cross-links would bend DNA by as much as 70 degrees [Peckler, S., Graves, B., Kanne, D., Rapoport, H., Hearst, J. E., & Kim, S.-H. (1982) J. Mol. Biol. 162, 157-172]. DNA can exist in a stably bent configuration in solution as recently demonstrated from analysis of polyacrylamide gel electrophoresis and differential decay of birefringence. Using these techniques, we have investigated the structure of DNA cross-linked with 8-methoxypsoralen and 4,5',8-trimethylpsoralen. The results are not consistent with cross-links introducing any appreciable stable bend in double-stranded DNA molecules. Results suggest that photobound 4,5',8-trimethylpsoralen molecules lengthen DNA by the equivalent of about one base pair per photobound adduct. We have also determined that 4,5',8-trimethylpsoralen cross-links are introduced preferentially into 5'-TA compared to 5'-AT DNA sequences.