Replication origins in metazoan chromosomes: fact or fiction?

The process by which eukaryotic cells decide when and where to initiate DNA replication has been illuminated in yeast, where specific DNA sequences (r eplication origins) bind a unique group of proteins (origin recognition com plex) next to an easily unwound DNA sequence at which replication can begin . The origin recognition complex provides a platform on which additional pr oteins assemble to form a pre-replication complex that can be activated at S-phase by specific protein kinases. Remarkably, multicellular eukaryotes, such as frogs, flies, and mammals (metazoa), have counterparts to these yea st proteins that are required for DNA replication. Therefore, one might exp ect metazoan chromosomes to contain specific replication origins as well, a hypothesis that has long been controversial. In fact, recent results stron gly support the view that DNA replication origins in metazoan chromosomes c onsist of one or more high frequency initiation sites and perhaps several l ow frequency ones that together can appear as a nonspecific initiation zone . Specific replication origins are established during G1-phase of each cell cycle by multiple parameters that include nuclear structure, chromatin str ucture, DNA sequence, and perhaps DNA modification. Such complexity endows metazoa with the flexibility to change both the number and locations of rep lication origins in response to the demands of animal development. (C) 1999 John Wiley & Sons, Inc.