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

• Published in: Methods in molecular biology (Clifton, N.J.) Vol. 2651; pp. 1 - 32
• Main Author: Jovin, Thomas M.
• Format: Book Chapter Journal Article
• Language: English
• Published: New York, NY Springer US 2023
• Series: Methods in Molecular Biology
• Subjects: CD left-handed DNA; DNA; DNA - genetics; DNA - metabolism; DNA, B-Form; Left-handed DNA; Nucleic Acid Conformation; Parallel-stranded ps; Phosphorothioate-modified Z-DNA; Polyribonucleotides; R–L transition of poly[d(G-C)]; TOP2A; Z-DNA; TOP2A; Left-handed DNA; R–L transition of poly[d(G-C)]; CD left-handed DNA; Phosphorothioate-modified Z-DNA; Z-DNA; Parallel-stranded psRR-DNA
• ISBN: 9781071630839; 1071630830
• ISSN: 1064-3745; 1940-6029
• DOI: 10.1007/978-1-0716-3084-6_1

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.