Mechanisms for Rep 1 icat ion Completing DNA

DNA replication consists of three steps: initiation, ongoing replication, and termination. The termination of replication is important because the synchrony of the termination process with subsequent cell division should be a significant factor in the equal and orderly distribution of genetic material to the daughter cells of both prokaryotes and eukaryotes. Termination in a circular chromosome in prokaryotes involves arrest of replication forks at specific sequences called replication arrest sites (for reviews of this process, see Hill 1992; Baker 1995). There are some exceptions to the phenomenon of sequence-specific replication arrest in both prokaryotic and eukaryotic chromosomes; e.g., the early stage of bacteriophage h DNA replication (Valenzuela et al. 1976) and SV40 DNA replication (Lai and Nathans 1975). Replication fork arrest is the first step in the termination process. Termination also involves, in Escherichia coli, decatenation of the arrested, catenated daughter molecules of DNA by a special topoisomerase called top0 IV (Kato et al. 1988, 1990; Schmid 1990; Adams et al. 1992; Hiasa and Marians 1994b). Mutants that are defective in top0 IV, a heterodimeric enzyme, are also defective in nucleoid segregation (Kato et al. 1988; Schmid 1990; Adams et al. 1992). More information on topoisomerases can be found in the chapter by Hangaard Andersen et al. (this volume). A third step in termination and proper segregation of the newly completed daughter molecules involves a site-specific recombination system. The system resolves multimers generated by an odd number of recombinations which may occur between the two separating daughter, circular DNA molecules (Blakely et al. 1991; Kuempel et al. 1991). Although a great deal is known about the termination of replication in prokaryotes, very little is known about this process in eukaryotes. In eukaryotic chromosomes, the linear DNA molecule faces two major problems for completing a round of replication. First, the newly synthesized strand at its 5 ' end would have a gap created by the removal of