Theoretical analysis of transitions between B- and Z-conformations in torsionally stressed DNA

Abstract

Recently, a new structure called Z-DNA has been proposed for alternating poly(dG-dC)·poly(dG-dC) sequences based on crystallographic analysis of the hexanucleotide¹. The Z-form is a left-handed double helix containing 12 base pairs per turn. In contrast, the Watson–Crick B-form helix is thought to have 10.4 pairs per turn of right-handed helix^2,3,8. A cooperative, salt-induced conformational transition has been observed in poly(dG-dC)·poIy(dG-dC)⁴, which has been interpreted as being between the B-form (low salt) and the Z-form (high salt)¹. We now analyse the possibility that such transitions could occur in susceptible sequences in physiological conditions as a consequence of the torsional stresses imposed by superhelicity. As in vivo DNA commonly occurs in a negatively supercoiled, hence underwound, state, these transitions could serve important biological functions. Both thermodynamic and statistical mechanical theories of stress-induced two-state transitions have been developed previously^5,6. Here we apply these theories to transitions between the B-form and the Z-form in regions of appropriate base sequence. Assuming that the unstressed duplex is entirely B-form, we show that when the molecule is constrained to be underwound, susceptible regions may transform to the Z-form, thereby absorbing most of the torsional deformation. Interestingly, this transition is relatively independent of temperature.