HENRY M. SOBELL

A MECHANISM TO UNDERSTAND THE COOPERATIVE BINDING
BY ETHIDIUM TO THE ALTERNATING d (G-C) POLYMER UNDER
HIGH SALT CONDITIONS



The alternating poly d (G-C) synthetic polymer undergoes the B- to Z- transition under high salt conditions. Under these conditions, ethidium demonstrates high cooperativity when binding to this polymer. What is the underlying mechanism for this transition?

These data indicate the presence of a structural phase transition, the emergent phase being the ethidium: (high-energy) beta-DNA complex.

The cooperative nature of the binding reaction is a direct result of the presence of high-energy phase boundaries that connect Z-DNA with B-DNA and their ease of movement. The phase transition begins with ethidium binding to small beta-DNA regions located within dislocaton pairs surrounding Z-DNA ("nucleation", see top illustrations). This is followed with the sequential binding by ethidium into expanding domains of beta-DNA, at the expense of Z-DNA ("propagation", see middle illustrations). Finally, extensive regions of this (neighbor-exclusion) ethidium: (high-energy) beta-DNA complex form that replaces Z-DNA (see bottom illustrations). As stated above, this mechanism is most easily understood as being a structural phase transition, in which the ethidium: (high-energy) beta-DNA complex emerges as the dominant phase. See data below, which shows the ethidium-poly d (G-C) cooperative binding isotherm under high salt conditions.