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How Different DNA-Binding Proteins Affect Long-Range Oxidative Damage to DNA

Rajski, Scott R. and Barton, Jacqueline K. (2001) How Different DNA-Binding Proteins Affect Long-Range Oxidative Damage to DNA. Biochemistry, 40 (18). pp. 5556-5564. ISSN 0006-2960. doi:10.1021/bi002684t.

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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 π-stack inhibit DNA charge transport. Alternatively, interactions that promote no helix distortion but, as a result of tight packing, may rigidify the π-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.

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Barton, Jacqueline K.0000-0001-9883-1600
Additional Information:© 2001 American Chemical Society. Received November 22, 2000; Revised Manuscript Received March 1, 2001. Publication Date (Web): April 12, 2001. Supported by NIH Grant GM49216. We thank our close co-workers Sanjay Kumar and Richard J. Roberts of New England Biolabs (Beverly, MA) for samples of wild-type and M.HhaI Q237W. We also thank Professor Carl S. Parker (Caltech) for the generous gift of ANTP-binding domain peptide and Professors John Horton and Xiaodong Cheng of Emory University for samples of R.PvuII.
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Issue or Number:18
Record Number:CaltechAUTHORS:20160209-152857175
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Official Citation:How Different DNA-Binding Proteins Affect Long-Range Oxidative Damage to DNA Scott R. Rajski and Jacqueline K. Barton Biochemistry 2001 40 (18), 5556-5564 DOI: 10.1021/bi002684t
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:64349
Deposited By: George Porter
Deposited On:09 Feb 2016 23:38
Last Modified:10 Nov 2021 23:29

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