DNA repair: CPR for the genome

DNA Damage and Repair: Vol. III Advances from Phage to Humansedited by Jac A. Nickoloff and Merl F. Hoekstra. Humana Press, 2001. £102/$135 hbk (xiv + 411 pages) ISBN 0 89603 803 3If you had a heart attack, you would hope someone would be quickly on hand to administer CPR. For the genome, the equivalent of a cardiac arrest is a stalled replication fork. It too needs fast resuscitation, as only then can it resume DNA replication – the central process in life.In the genome, such emergencies are handled by an intricate network of DNA-repair pathways. These form parts of a highly coordinated cellular response to genomic stress. Genomic stress caused by cellular processes, spontaneous decay of DNA and extrinsic DNA-damaging agents is as old as life itself. Indeed, cells can cope remarkably well with this stress – unlike some researchers for whom the stresses of life (e.g. grant deadlines) sometimes lead to near heart attacks.Even in a fast-moving field such as DNA repair, learned reviews that provide a balanced and scholarly assessment of the literature still occupy an important place. There is much here for interested readers who find themselves lost in the vast literature of this field. In both this and the previous two volumes, the reviews are mostly well written and authoritative, and they reflect the state of the art as of the late 1990s. In fact, some references are as recent as the year 2000 in volume three – an impressive feat for a book that appeared in early 2001.The first two volumes were competently reviewed previously 1xNo hedging on DNA repair. Wood, R.D. Trends Genet. 1998; 14: 433–434Abstract | Full Text | Full Text PDFSee all References1, and they comprise a nearly comprehensive resource. The third volume closes some of the previously noted – and acknowledged – gaps in coverage by providing chapters on important model systems (e.g. bacteriophage, Drosophila), as well as including some on structural biology (e.g. human AP endonuclease); this last topic is an aspect that is certain to expand in the future.This volume contains 15 contributions with a focus on double-strand break repair, a particularly vibrant area of DNA repair. One of the crucial developments in this area was the discovery in bacteria and phage (yes, bacterial and phage research still leads the way!) that replication forks stall and need to be restarted to complete DNA replication. The restart occurs by a complex and poorly understood mechanism termed recombination-dependent replication, which involves homologous recombination. Progress in the understanding of the functions of individual components and of the overall mechanism of double-strand break repair has been truly impressive in the past few years. This progress, based on the individual strengths of different model systems, as represented by E. coli, yeast, Drosophila and mammals, is well documented in several chapters. A chapter on the evolutionary conservation of eukaryotic DNA repair mechanisms puts this into a broader perspective.The roles of the Brca1 and Brca2 tumor suppressor proteins in DNA repair are still mysterious, but the relevant chapter provides a balanced and informative discussion of the literature up to 1999. The contributions on the cross-talk between DNA repair and other cellular processes such as telomere maintenance, cell-cycle checkpoints, immunoglobulin rearrangements, and development, each reveal important interconnections, some of which are well known, whereas others are quite surprising and novel. Much of the focus in the DNA repair field has been on the mechanisms of the different repair pathways. However, the chapter on the regulation of DNA repair and recombination by the yeast mating-type locus approaches the important question of how DNA repair is regulated.DNA repair is too large and fast-moving a field to be completely and accurately covered in a multi-author collection of reviews like this. Consequently, some sections have already been overtaken by recent results. Not all chapters are equally well balanced, written, referenced or illustrated, but this generic criticism should not distract from the wonderful service the editors and contributors have done for the DNA repair community. They have succeeded in providing authoritative and reflective summaries on topics that move this field.