10 Temporal Order of DNA Replication

Abstract

BASIS OF THE REPLICATION TIMING PROGRAM Chromosomal DNA is replicated according to a specific temporal program in virtually all eukaryotic cells. In typical metazoan somatic cells, the DNA replication period is several hours in length, with some sequences reproducibly replicating at the beginning of the S-phase period and others replicating much later (Balazs et al. 1974; Goldman et al. 1984; Hatton et al. 1988; Lucas and Feng 2003). Single-celled eukaryotes such as yeast also replicate their DNA according to a reproducible program, even though their S-phase duration is measured in minutes rather than hours (Reynolds et al. 1989). Eukaryotic chromosomes are replicated from multiple origins, so the replication program could in principle reflect either temporally regulated origin initiation or regulation of the progression rate of replication forks. Although cases of regulated fork progression clearly exist (Brewer and Fangman 1988; Linskens and Huberman 1988; Lopez-Estrano et al. 1998, 1999; Maric et al. 1999; Norio et al. 2000; Cha and Kleckner 2002), the replication program is based primarily on different activation times of the various replication origins (Ferguson et al. 1991; Ferguson and Fangman 1992). In this chapter, we outline recent discoveries concerning the control of initiation time of replication origins during S phase. Origin specification and activation are best understood in Saccharomyces cerevisiae , and it is in this organism that we have the most advanced understanding of the control of the replication temporal program. We compare findings in yeast with those derived from other eukaryotic systems to illustrate the similarities—and...