Genetic dissection of a mammalian replicator in the human beta-globin locus

Science. 1998 Aug 14;281(5379):1005-9. doi: 10.1126/science.281.5379.1005.


The timing and localization of DNA replication initiation in mammalian cells are heritable traits, but it is not known whether initiation requires specific DNA sequences. A site-specific recombination strategy was used to show that DNA sequences previously identified as replication initiation sites could initiate replication when transferred to new chromosomal locations. An 8-kilobase DNA sequence encompassing the origin of DNA replication in the human beta-globin locus initiated replication in the simian genome. Specific deletions within the globin origin did not initiate replication in these chromosomal sites. These data suggest that initiation of DNA replication in mammalian cells requires specific sequence information and extend the replicon hypothesis to higher eukaryotes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Line
  • Chlorocebus aethiops
  • DNA / genetics
  • DNA Nucleotidyltransferases / metabolism
  • DNA Replication*
  • Gene Targeting
  • Globins / genetics*
  • Humans
  • Integrases / metabolism
  • Polymerase Chain Reaction
  • Replication Origin*
  • S Phase
  • Sequence Deletion
  • Viral Proteins*


  • Viral Proteins
  • Globins
  • DNA
  • Cre recombinase
  • DNA Nucleotidyltransferases
  • FLP recombinase
  • Integrases