Salt-dependent dynamic structure of poly(dG-dC) · poly(dG-dC)

Abstract

Until recently, all known nucleic acid duplex helices were thought to be conformationally related to A DNA or B DNA, these right-handed helices being characterized by C(3′) endo or C(2′) endo pucker for the respective sugar residues and by an antiglycosidic bond¹. This situation has since drastically changed, for X-ray studies on crystals of alternating d(CpG) DNA fragments have demonstrated the existence of a left-handed double helix, termed Z DNA (ref. 2). In this novel double helix the base-pairing is of Watson–Crick type, but the cytidine and guanosine residues have the anti and syn conformations, respectively, and thus the repeating unit is two base pairs. Such a left-handed helix can also account for the X-ray diffraction pattern of alternating poly(dG-dC) ∣ poly(dG-dC) fibres³. However, Pohl and Jovin have shown that in solution poly(dG-dC) ∣ poly(dG-dC) undergoes a salt-induced cooperative transition⁴. It is very likely that the left-handed double helix is relevant to the high-salt conformation of poly(dG-dC) ∣ poly(dG-dC) and that the low-salt conformation of poly(dG-dC)∣ poly(dG-dC) belongs to the B-DNA family^3,5. The techniques previously used to study the salt-induced transition of poly (dG-dC) ∣ poly (dG-dC) in solution—circular dichroism (CD), absorption spectroscopy⁴ and nuclear magnetic resonance⁵—give essentially a static picture of the conformation of the molecule. Such information, although fundamental, is incomplete because double-helical nucleic acids in solution are known to be subjected to thermal fluctuations resulting in transient conformations with opened base pairs^6–9. A particularly useful probe of the dynamic aspects of nucleic acid structure is the tritium exchange technique largely developed by Englander and colleagues¹⁰. We have now used this technique to study the dynamic structure of poly(dG-dC) · poly (dG-dC) and have found that this varies depending on whether high or low salt conditions are used.