Novel DNA Polymerases Offer Clues to the Molecular Basis of Mutagenesis

through sites of stalled or blocked DNA replication (repli-cative bypass or translesion DNA synthesis) (Friedberg et al., 1995). However, until recently, understanding exactly how the products of SOS-induced genes modify the replicative machinery to facilitate error-prone transle-sion synthesis has posed a formidable biochemical challenge. Even less was known about how such gene products might participate in the spontaneous generation of In his text entitled " The Molecular Basis of Mutation " mutations. " ever since mutation was emphasized by de Vries (1901) also see Walker, 1998) have reconstituted replicative as a fundamental genetic process, its analysis has occu-bypass of sites of base damage in DNA with purified E. pied a position close to the center of the geneticist's coli proteins. One of these studies (Tang et al., 1998) arena. " The ensuing three decades have witnessed the demonstrated a requirement for DNA polymerase III ho-identification of a large array of genes which participate loenzyme, the primary DNA replicative enzyme in E. coli in both spontaneous mutagenesis and that associated (or DNA polymerase II); activated RecA protein, a multi-with deliberate exposure to DNA-damaging agents in functional protein required for regulation of the SOS the prokaryote E. coli (Table 1). An equally impressive response, genetic recombination, and mutagenesis in E. list of genes has emerged from analysis of the yeast S. coli (Friedberg et al., 1995); single-strand binding protein cerevisiae (Table 1). However, whereas the advent of (SSB); and UmuDЈ 2 C (a complex comprised of two mole-recombinant DNA technology and the almost facile over-cules of proteolytically processed UmuD protein and expression of cloned genes has greatly facilitated the one molecule of UmuC protein; Walker, 1998; Figure transition from genetics to biochemistry in the fields 1A). The precise functions of these latter proteins are of DNA replication, transcription, recombination, and unknown. Surprisingly, these studies also revealed low repair, the biochemical bases of mutagenesis have seri-levels of replicative bypass with purified UmuDЈ 2 C com-ously lagged behind. A number of recent advances, in plex in the absence of DNA pol III core enzyme. However, particular the identification and characterization of sev-primer extension beyond sites of bypass was consider-eral novel DNA polymerases (and the prospect of an ably enhanced by the additional presence of DNA pol even larger number remaining to be characterized), have III core enzyme, DNA pol III ␣ subunit, or purified DNA illuminated several aspects of mutagenesis in lower and pol …