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1 Duplication of DNA in Eukaryotic Cells

Thomas J. Kelly, Bruce Stillman


Many of the most basic biochemical mechanisms of DNA replication have been conserved from prokaryotes to eukaryotes, but the evolution of eukaryotic cells resulted in many changes in the logic of the cell cycle and in the mechanisms that regulate DNA replication. In a prokaryotic cell, such as Escherichia coli, DNA replication is generally initiated at a single essential locus in the circular chromosome (replicator). The timing and specificity of initiation are determined by the binding of a protein complex (initiator) to specific sequences in the replicator (Jacob et al. 1964). In a rapidly growing E. coli cell, initiation events occur at intervals significantly shorter than the time required to complete the synthesis of daughter chromosomes. Under these circumstances, DNA synthesis is essentially continuous throughout the cell cycle, and cells contain several partially completed chromosomes. In contrast, in eukaryotic cells, DNA replication occupies only part of the cell cycle and alternates with mitosis. Moreover, each chromosome is duplicated only once in each cell cycle, producing two complete daughter chromosomes. To ensure the timely completion of the replication of the large genomes of eukaryotes, initiation of DNA synthesis occurs at multiple chromosomal sites (Huberman and Riggs 1966). The number of such origins of DNA replication ranges from a few hundred in a yeast cell to tens of thousands in a human cell. Given the complexity of genome duplication in eukaryotic cells, it is not surprising that novel regulatory mechanisms have evolved to coordinate DNA replication with other events in the cell...

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