Effect of Base Composition on DNA Bending by Phosphate Neutralization

Of the many forces involved in DNA bending by proteins, we have focused on the possible role of asymmetric phosphate neutralization due to interactions between the negatively charged phosphate backbone of duplex DNA and cationic amino acids of an approaching protein. The resulting unbalanced charge distribution along the duplex DNA is thought to induce the double helix to collapse toward the neutralized surface. Previous work has confirmed that DNA bending (approximately 20.7 +/- 4 degrees) is induced by asymmetric incorporation of six uncharged racemic methylphosphonate analogs partially neutralizing one face of GC-rich duplex DNA. We have now analyzed DNA duplexes with similar patches of methylphosphonate linkages in an AT-rich sequence context and again observe bending toward the neutralized face, to an extent (20 +/- 0.6 degrees) 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 propensity of A-T base pairs to roll toward the minor groove in the tested sequences.