Michael Waring—A scientific life in DNA

Abstract

During a long and extremely productive scientific life Michael Waring made substantial contributions to the understanding of certain fundamental physical properties of the DNA double helix. In this review I summarize his early studies on DNA supercoiling and his later conclusions on the role of natural DNA base analogues in determining DNA stiffness and nucleosome positioning. The latter are reassessed in the context of subsequent advances in the understanding of the parameters affecting base-step deformability. Michael's scientific career spanned nearly six extremely productive decades. He started out soon after the double-helical structure of DNA was proposed by Watson and Crick, in 1953. And from then on DNA was always the main focus of his research, with an especial interest in the mechanism of how DNA-binding drugs interacted with the genetic material. In this retrospective on Michael's science I shall concentrate on his contributions to the understanding of DNA structure and function rather than his voluminous exploration of drug-DNA interactions. The latter, I'm sure, will be discussed by those more intimately involved in those experiments. 2 | DNA SUPERCOILING I first became aware of Michael's science in the mid-1960s when I was working as a research student at the Medical Research Council Laboratory of Molecular Biology (MRC-LMB) in Cambridge, England. I was studying the initiation of transcription on polyoma DNA which had very kindly been provided by Lionel Crawford (then at the Institute of virology in Glasgow, Scotland) and I saw that Michael was scheduled to present a Tea Club in the University of Cambridge Department of Biochemistry on the interaction of ethidium bromide with polyoma DNA. Michael had newly returned from a post-doctoral stint at the Carnegie Institute in Washington DC, USA in the group of Roy Britten and had taken up a University Demonstratorship in the Department of Biochemistry, resuming his pre-doctoral interest in antimicrobial agents that bind DNA.At the Tea Club Michael recounted the successful outcome of the confluence of his and Lionel's research interests. Ethidium bromide is a phenanthridine trypanocide which forms a complex with doublestranded DNA. [1,2] By analogy with Leonard Lerman's work on the mode of acridine binding to DNA, [3] Michael, together with Watson