Origins of DNA replication in metazoan chromosomes.

In metazoan chromosomes, initiation of DNA replication occurs primarily at specific sites (0.5-3 kb; the OBR) using the same replication fork mechanism favored by simple genomes. Nucleosome segregation is distributive. However, initiation events also occur at other sites randomly distributed throughout a larger initiation zone (8-55 kb). These nonspecific initiation events presumably occur at a lower frequency than those at the OBR. Although origins in native chromosomes appear to be genetically determined, ori sequences have been convincingly demonstrated only during programmed gene amplification. It seems likely that metazoan origins include both specific DNA sequences as well as chromatin structure and nuclear organization, something that may be difficult to reproduce with plasmid DNA. Definitive answers will come only with a functional assay for initiation that exhibits the sequence-specific characteristics observed in vivo.