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The Fixer

Ben Van Houten

DNA Damage and Repair. 2 vols. DNA Repair in Prokaryotes and Lower Eukaryotes; DNA Repair in Higher Eukaryotes. Jac Nickoloff and Merl Hoekstra, eds. 626 and 672 pp. Humana Press, 1998. $250 (set).

The capacity to blunder slightly is the real marvel of DNA. Without this special attribute, we would still be anaerobic bacteria, and there would be no music.

—Lewis Thomas, The Medusa & the Snail

The symphony of life is genetically scored as a long sequence of bases in DNA. As life evolved on earth it had to cope with environmental chemicals and physical agents that can directly damage DNA. All organisms studied to date have a series of complex protein machines that survey the strands of DNA, identifying and removing damaged or mispaired bases. The wonder and beauty of life is that DNA repair is precise enough to allow complex organisms to function normally yet accept a low level of mistakes that permits natural selection and evolution.

The concept of DNA repair was developed almost simultaneously with the Watson and Crick structure of DNA, as the one strand serves as information for fixing the other. However, it was not until the late 1980s and early '90s that molecular biologists found DNA repair to be intimately linked to other DNA transactions in the cell, such as DNA replication and transcription. In 1994 the journal Science, in recognition of the growing interest in DNA repair and its impact on a large number of diseases, voted the family of proteins that mediate DNA repair as the molecules of the year. It was during a meeting of the same year that Jac A. Nickoloff and Merl F. Hoekstra, editors of DNA Damage and Repair, began to plan a comprehensive review of the field. The following year, the wonderful second edition of Errol Friedberg, Graham Walker and Wofram Seide's DNA Repair and Mutagenesis, the only textbook on the subject, appeared.

As the editors of this new work pose in their preface, why write another book on DNA repair? The intricate details of the molecular biology of DNA repair are rapidly evolving, and it was the goal of this two-volume set to allow the specialist and others to have a thorough understanding of how DNA damage arises and of the nature of the proteins that fix the damage. DNA Damage and Repair is organized into one volume dedicated to prokaryotes and lower eukaryotes (I'm not sure if frogs would agree with this designation) and a second volume for higher eukaryotes. The editors have enlisted a legion of experts to contribute 51 chapters. The set is introduced by one of the founders of the field of DNA repair, Phil Hanawalt, who in 1979, in the span of only 53 pages, was able to cover the entire field in Annual Reviews of Biochemistry. So what has happened to the field of DNA in the past 20 years that warrants more than 1,200 pages?

There have been four major advances that have led to this treasure trove of information. First, the Herculean task of identifying, purifying and characterizing each gene product responsible for each step in the pathway has culminated in the in vitro biochemical reconstruction of several repair processes found in bacteria, yeast and human beings. This crowning achievement is truly one of the marvels of modern molecular biology and is well documented in these two volumes. Second, studies of human patients and knock-out mice defective in specific steps in repair have shown that alterations in specific repair systems can lead to various diseases including cancer, neurodegeneration and premature-aging syndromes. This too is nicely covered. A third emerging field, which the editors apologize in the preface for not detailing sufficiently, is the use of nuclear magnetic resonance and x-ray diffraction techniques that have lead to an understanding of the three-dimensional structure of DNA damage and the proteins that act on these lesions. A fourth area that is well treated here is the complex cascade of cellular responses to DNA, which include signal-transduction pathways, alterations in gene expression, changes in cell-cycle kinetics and programmed cell death, or apoptosis.

Books on any fast-moving field run the risk of becoming rapidly outdated, but these volumes will serve as an important resource to repair aficionados and novices alike for some time to come. In this regard, it is interesting to note that a colleague of mine and I recently traveled to Japan to visit a number of laboratories working on DNA repair. Although my friend left his English-Japanese dictionary and even his umbrella in the States, he made sure to pack this bulky set to read on the plane and in his free time between lectures, sushi, sake and karaoke.—Ben Van Houten, Sealy Center for Molecular Science, University of Texas Medical Branch at Galveston, and National Institute of Environmental Health Sciences

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