EFFECT OF BASE COMPOSITION ON DNA BENDING BY PHOSPHATE NEUTRALIZATION

Of the many forces involved in DNA bending by proteins, we have focuse d on the possible role of asymmetric phosphate neutralization due to i nteractions between the negatively charged phosphate backbone of duple x DNA and cationic amino acids of an approaching protein. The resultin g unbalanced charge distribution along the duplex DNA is thought to in duce the double helix to collapse toward the neutralized surface. Prev ious work has confirmed that DNA bending (similar to 20.7 +/- 4 degree s) is induced by asymmetric incorporation of six uncharged racemic met hylphosphonate analogs partially neutralizing one face of GC-rich dupl ex DNA. We have now analyzed DNA duplexes with similar patches of meth ylphosphonate linkages in an AT-rich sequence context and again observ e bending toward the neutralized face, to an extent (20 +/- 0.6 degree s) comparable to that observed for neutral patches in GC-rich DNA. The similar induced bend angles in AT-rich and GC-rich contexts does not reveal increased flexibility in AT-rich sequences, or a particular pro pensity of A-T base pairs to roll toward the minor,groove in the teste d sequences. (C) 1998 Published by Elsevier Science B.V. All rights re served.