DNA: 60 years of the structure of life

Abstract

In April 1953 a breathtaking scientific race came to its conclusion with the co-publication of a triumvirate of papers in Nature, which together proposed the now-iconic structure of DNA. That double-helical model, as first drawn in Watson and Crick's portion of the trifecta, has remained fundamentally unchanged over the past 60 years. It is nearly impossible to overstate the importance of this structure in modern biochemistry and molecular biology. As Sir Lawrence Bragg stated in his introduction to Jim Watson's rousing first-person account of the discovery, The Double Helix, “The number of researches which it has inspired is amazing; it has caused an explosion in biochemistry which as transformed the science.” In time for the 50th anniversary of the award of the Nobel Prize for this work, TiBS editorial board member Jan Witkowski recently co-edited a remarkable new version of The Double Helix that includes more details and documentation of the history than ever, termed The Annotated and Illustrated Double Helix. Here, TiBS celebrates the discovery with a special focus issue dedicated to DNA.The iconic nature of the double-helix can best be illustrated by the size of the splash made by any new research demonstrating an alternative DNA structure. For instance, recent work by Shankar Balasubramanian showing in vivo evidence for the widespread existence of quadruplex DNA structures in human cells was picked up by major media outlets, including Fox, NBC, and The Huffington Post. Although these structures are far from the norm, they have important biological implications. We begin this issue by talking to Dr. Balasubramanian, and he tells us about when and where these structures can be found, and their potential biological consequences.In his Trendstalk, Dr. Balasubramanian states that one of the exciting current frontiers of DNA research stems from the observation that several new DNA base modifications exist. Some of these modifications, such as 5-hydroxymethylcytosine, are the results of enzyme-catalyzed oxidation of methylated DNA. Interestingly, in this issue Dr. Albert Jeltsch proposes that it was evolution of enzymes that can oxidize methylation marks, both on DNA and histone proteins, which enabled the explosion of multicellular animal life during the Cambrian era.DNA methylation marks are found throughout the genome, and they are generally thought to control gene expression. However, the mechanisms through which methylated DNA is specifically recognized by proteins that confer changes in gene expression have remained unclear. In this issue, Cheng et al. examine recent studies and propose a common recognition mode for 5-methylcytosine (5mC) that involves a 5mC-Arginine-Guanine triad.Additionally, this issue includes two Reviews on one of the most fundamental properties of DNA: its ability to replicate. Bielinsky et al. discuss the enigmatic protein Mcm10, which has been shown to be required for genome replication in eukaryotes. Its exact function is unclear, but the authors provide a cohesive analysis of the different models and persistent controversies. Finally, O’Donnell et al. provide an insightful update on the composition and mechanisms of the replisome, the complex molecular machine that carries out replication of DNA. In their review they highlight the recent paradigm-shifting discoveries, such the finding that the bacterial replisome consists of three DNA polymerases, not two.Collectively, these articles highlight some of the rapidly progressing areas of DNA research. No doubt none of the science presented here would have been possible without the insight gained from knowledge of the structure of DNA. We hope that you enjoy this collection of articles on this, the 60th anniversary of the discovery of the structure of DNA, and we look forward to seeing what the next 60 years of DNA research will bring.