DNA Repair in the 1990s DNA Damage and Repair Volume 1: DNA Repair in Prokaryotes and Lower Eukaryotes Volume 2: DNA Repair in Higher Eukaryotes Edited by Jac A. Nickoloff and Merl F. Hoekstra Totowa, NJ: Humana Press (1998). Vol. 1, 626 pp. $125.00; Vol. 2, 639 pp. $125.00

transcriptional events, including not only its named fact, a survey of OMIM reveals that of the human genetic function as a coactivator for the phosphorylated form diseases for which genes are identified, only a small of CREB (cAMP response element–binding protein), but minority are caused by mutations in genes encoding also the regulation of histone acetylation. Yet while inhi-transcription factors. While the restricted focus of this bition of expression of a C. elegans CBP homolog results work on transcription factors is pragmatic, it is also thus in a complete absence of somatic morphogenesis, intra-somewhat contrived. For example, the text describes genic mutations in human CBP are associated with a the involvement of the MSX2 homeobox gene in Boston-comparatively restricted phenotype, Rubinstein-Taybi type craniosynostosis, a disorder characterized by pre-syndrome, a dysmorphosis characterized by specific mature fusion of the sutures of the newborn skull. The limb and craniofacial defects and mental retardation. more frequent and better-characterized craniosynos-Since these genes are members of multigene families— tosis syndromes, however, are due to mutations in three CBP shares homology with another coactivator, P300, of the FGF receptor genes. Left unexplored is what rela-while XH2 is a member of the helicase superfamily—their tion, if any, exists between FGF signaling and MSX2 in restricted mutant phenotypes might be explained on the sutural biology. Ideally, the molecular function of tran-basis of functional redundancy. What seems equally scription factors is best understood in the context of likely, however—if unpleasantly more complex—is that their biologic function, and vice versa. it is the function of the gene product in the context of Currently, the number of human genetic diseases the specific biology of the organism that dictates listed in OMIM exceeds 10,000. As more and more dis-whether and what identifiable phenotype will result. ease-producing genes are identified, an attractive pros-Interestingly, Rubinstein-Taybi syndrome has been pect for the future is their integration—whether they associated at low frequency with a variety of other con-encode transcription factors or not—into specific path-genital malformations, raising the possibility that the ways based on the analysis of their respective mutant phenotypic expression of this disease results from poly-phenotypes. Of course, studies in humans are necessar-morphic differences in the expression levels of other ily limited in their potential for embryologic and genetic genes whose products interact with CBP. In the future, investigation, but they do provide a powerful starting it can be anticipated that the identification of disease point. …