How different DNA-binding proteins affect long-range oxidative damage to DNA.
Here the effect on DNA-mediated charge transport of binding by a variety of proteins is examined. DNA assemblies were constructed that contain a tethered rhodium intercalator, as photooxidant, as well as two 5'-GG-3' sites flanking the DNA-binding site for the different proteins. By monitoring the ratio of oxidative damage promoted at the guanine doublet situated distal to the protein-binding site versus that at the proximal site as a function of protein binding, the effects of binding the proteins on DNA-mediated charge transport were determined. Proteins examined included both the wild-type and mutant methyltransferase, M.HhaI, which are base-flipping enzymes, the restriction endonuclease R.PvuII, a TATA-binding protein, which kinks the DNA, and the transcription factor Antennapedia homeodomain protein, which binds DNA through a helix-turn-helix motif. In general, it was observed that yields of long-range oxidative damage correlate with protein-dependent alterations in DNA base stacking. Interactions that disturb the DNA pi-stack inhibit DNA charge transport. Alternatively, interactions that promote no helix distortion but, as a result of tight packing, may rigidify the pi-stack, serve instead to enhance the ability of the DNA base pairs to serve as a conduit for charge transport. Thus, protein binding to DNA modulates long-range charge transport both negatively and positively, depending upon the specific protein/DNA interactions in play. Long-range DNA charge transport and this modulation by protein binding may be important to consider physiologically.
Rajski
S R
SR
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena 91125, USA.
Barton
J K
JK
D051943:Antennapedia Homeodomain Protein; D020137:Base Pair Mismatch; D001665:Binding Sites; D004247:DNA / Q000737:chemistry*; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000737:chemistry*; D015257:DNA-Cytosine Methylases / Q000737:chemistry; D015252:Deoxyribonucleases, Type II Site-Specific / Q000737:chemistry; D018398:Homeodomain Proteins / Q000737:chemistry; D007364:Intercalating Agents / Q000737:chemistry; D009687:Nuclear Proteins; D009690:Nucleic Acid Conformation; D010083:Oxidants, Photochemical; D011994:Recombinant Proteins / Q000737:chemistry; D035181:TATA-Box Binding Protein; D014157:Transcription Factors / Q000737:chemistry
D051943:Antennapedia Homeodomain Protein; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D007364:Intercalating Agents; D009687:Nuclear Proteins; D010083:Oxidants, Photochemical; D011994:Recombinant Proteins; D035181:TATA-Box Binding Protein; D014157:Transcription Factors; D004247:DNA; C037664:DNA modification methylase HhaI; D015257:DNA-Cytosine Methylases; C061224:endodeoxyribonuclease PvuI; D015252:Deoxyribonucleases, Type II Site-Specific