The Origin of Left-Handed Poly[d(G-C)]

The discovery of a reversible transition in the helical sense of a double-helical DNA was initiated by the first synthesis in 1967 of the alternating sequence poly[d(G-C)]. In 1968, exposure to high salt concentration led to a cooperative isomerization of the double helix manifested by an inversion in the CD spectrum in the 240-310 nm range and in an altered absorption spectrum. The tentative interpretation, reported in 1970 and then in detailed form in a 1972 publication by Pohl and Jovin, was that the conventional right-handed B-DNA structure (R) of poly[d(G-C)] transforms at high salt concentration into a novel, alternative left-handed (L) conformation. The historical course of this development and its aftermath, culminating in the first crystal structure of left-handed Z-DNA in 1979, is described in detail. The research conducted by Pohl and Jovin after 1979 is summarized, ending with an assessment of "unfinished business": condensed Z*-DNA; topoisomerase IIα (TOP2A) as an allosteric ZBP (Z-DNA-binding protein); B-Z transitions of phosphorothioate-modified DNAs; and parallel-stranded poly[d(G-A)], a double helix with high stability under physiological conditions and potentially also left-handed.