DNA‐sequence binding preference of the GC‐selective ligand mithramycin: Deoxyribonuclease‐I/deoxyribonuclease‐II and hydroxy‐radical footprinting at CCCG, CCGC, CGGC, GCCC and GGGG flanked by (AT)_n and A_n· T_n

Carpenter, Mark L., Marks, Jonathan N. and Fox, Keith R. (1993) DNA‐sequence binding preference of the GC‐selective ligand mithramycin: Deoxyribonuclease‐I/deoxyribonuclease‐II and hydroxy‐radical footprinting at CCCG, CCGC, CGGC, GCCC and GGGG flanked by (AT)_n and A_n· T_n. European Journal of Biochemistry, 215 (3), 561-566. (doi:10.1111/j.1432-1033.1993.tb18066.x).

Abstract

We have used hydroxy‐radical and deoxyribonuclease‐I footprinting to probe the interaction of mithramycin with DNA fragments containing the sequences (AT)₁₀X(AT)₁₀ (X = CCCG, CCGC or CGGC) and A₁₄GCCCT₁₅. As expected the drug produces clear footprints located around the central four GC base pairs. The exact position of the footprint is different for the four sequences; the footprint with CCCG is displaced by two base pairs in the 5′ direction relative to GCCC. These variations are explained by suggesting that mithramycin avoids the dinucleotide CG and binds better to GG/CC than GC. Although there is little change in deoxyribonuclease‐I cleavage of the surrounding blocks of (AT)_n. cleavage by deoxyribonuclease II is markedly enhanced and certain thymines on the 5′ side of the ligand‐binding site become hyperreactive to hydroxy‐radical attack. Adjacent regions of A_n· T_n show enhanced rates of deoxyribonuclease‐I cleavage in the presence of the antibiotic.

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Contributors

Author: Keith R. Fox

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