On the nature of replication origins in higher eukaryotes

Establishing whether DNA replication in higher eukaryotic cells is regulated by genetic replicators has been one of the more challenging problems in cell biology. Several important replicon-mapping techniques have been developed in the past decade that have opened up new windows on replication origins. In the past few years, the application of these strategies has identified a large number of origins in a variety of different loci and organisms. Comparison of sequence motifs and chromosomal milieu, as well as genetic manipulation, should begin to uncover the secrets of these illusive regulatory elements.