GENETIC DISSECTION OF A MAMMALIAN REPLICATOR IN THE HUMAN BETA-GLOBINLOCUS

The timing and localization of DNA replication initiation in mammalian cells are heritable traits, but it is not known whether initiation re quires specific DNA sequences. A site-specific recombination strategy was used to show that DNA sequences previously identified as replicati on initiation sites could initiate replication when transferred to new chromosomal Locations. An 8-kilobase DNA sequence encompassing the or igin of DNA replication in the human P-globin Locus initiated replicat ion in the simian genome. Specific deletions within the globin origin did not initiate replication in these chromosomal sites. These data su ggest that initiation of DNA replication in mammalian cells requires s pecific sequence information and extend the replicon hypothesis to hig her eukaryotes.