Journal of Heredity 2003:94(4)
© 2003 The American Genetic Association 94:360-361
Book Review |
Anatomy of Gene Regulation: A Three-Dimensional Structural Analysis
Department of Molecular Biology and Pharmacology Washington University School of Medicine St. Louis, MO 63110
Panagiotis A. Tsonis. Cambridge University Press, Cambridge, U.K. 2003. 282 pp. $50.00.
Structural biology has revolutionized the way biological questions are approached and the detail with which cellular phenomena are understood. The DNA double helix, the first structure of a biological molecule, was determined by X-ray crystallography in 1953. Seven years later, our first glimpses of the X-ray structures of both myoglobin and hemoglobin were revealed. Since these monumental strides, the field of structural biology has exploded. In 2002, 3,381 new structures were deposited in the Protein Data Bank, raising the tally to 20,317 total structures available to date. There are more than 15 structural genomics projects presently under way in North America alone, with focuses on bacterial, plant, and human protein targets. It is clear that the age of structural biology is upon us. Researchers and students from all disciplines are increasingly benefiting from the three-dimensional intricacies of the molecules they study and appreciating the valuable information garnered through high-resolution structure determination. In Anatomy of Gene Regulation, the fundamentals of gene regulation are described using the known three-dimensional structures of the proteins and nucleic acids involved.
The text is introduced with a brief explanation of the structure determination methods of X-ray crystallography and nuclear magnetic resonance (NMR). The introduction is crafted with the nonstructural biologist in mind. Tsonis, himself not a structural biologist, does not litter the introduction with complex formulas and derivations that often intimidate nonexperts. One weakness I noticed was the cursory comparison of X-ray crystallography and NMR. The text would benefit from a description of how these methods can be complementary to one another and the type of information each method is best at providing. In addition, this information could aid the reader in better evaluating the presented structures and thinking critically about the information they reveal.
The book is divided into 11 chapters beginning with the organization of the genome and the structure of DNA, followed by sections on DNA replication, transcription, and protein translation, and concludes with a brief excerpt on protein folding and degradation. Each chapter opens with a "primer" that familiarizes the reader with the topics covered in the upcoming chapter. The book is filled with colorful figures, often in stereo, exhibiting proteins and nucleic acids in all their three-dimensional glory. Almost exclusively, the models are taken from the primary literature in which they were described. Therefore some figures are extremely clear and informative, whereas others are of lower resolution, much too small, and thus hard to extract all the useful information. Furthermore, many of the accompanying legends are brief and not very informative, forcing the reader to rake through the text to decipher the figures. However, all figures are well referenced, allowing the motivated reader to uncover additional information.
Sections of the text really shine, highlighting the power of structural biology in understanding biological mechanisms. A crystal structure of the prokaryotic transcription terminator Rho with bound oligocytosine sheds light on the molecular mechanism for Rho's preference for pyrimidine over purine. A detailed view reveals that key residues of Rho interact with cytosine similarly to the traditional cytosine-guanine base pairing, providing a nice example of a common theme in biology, molecular mimicry. In the section on DNA replication, the structure of the yeast topoisomerase II is presented. A heart-shaped molecular donut, the topoisomerase II dimer boasts an electropositive tunnel, the likely passage point for DNA. Based on crystallographic data, a model is presented that details the dynamics of topoisomerase II motion required for function. This example allows the reader to understand the living, breathing nature of enzymes instead of viewing proteins as static entities. The section closes with the structure of a DNA-tamoxifen (a potent anticancer compound) adduct. With a native DNA double helix shown alongside for direct comparison, the tamoxifen-induced distortion of DNA is obvious. As this structure demonstrates, structural biology is an important tool to identify and improve upon the action of potential therapeutic agents. The brevity of the text (only 257 pages) does not diminish from its impact, as some figures are worth a thousand words. In the section on eukaryotic transcription, the structure of a leucine zipper dimer snaked around a DNA double helix provides a vivid image of how these proteins interact with and affect DNA.
Unfortunately some structures are presently in a mainly descriptive fashion in which limited mechanistic or dynamic information is revealed. Often a deficiency in additional structures of these molecules in different catalytic states is to blame. Other sections lose focus or seem to be out of place in the text. The section on compartmentalization of transcription does not provide a single structure. The final section on birth and death of proteins is extremely cursory, excluding some exciting structural strides in this field.
This book is best used as a supplement to a more comprehensive text since many processes of gene regulation are described assuming the reader has a firm grasp of the fundamentals. However, Anatomy of Gene Regulation is an important resource for those seeking atomic resolution explanations for many gene regulatory processes and is a powerful teaching tool to expose students to the inner workings of gene regulation.
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