HOW IS A CYCLE OF DNA-REPLICATION INITIAT ED IN EUKARYOTES

important progress in the understanding of the mechanisms which contro l the initiation of DNA replication in eukaryotes has been made in the past few years. DNA replication origins have been precisely character ised in the yeast Saccharomyces cerevisiae and much effort has been ma de in trying to identify their counterparts in metazoans. During the c ell cycle, many protein complexes associate with replication origins a nd play a major role in the regulation of DNA replication. The Origin Recognition Complex (ORC) recognises and binds to replication origins throughout the cell cycle. In G1 phase, the Cdc6 protein and the prote ins of the MCM family (mini-chromosome maintenance 2-7) also bind to t he chromatin. Thus, these protein complexes associate sequentially wit h the chromatin and are all necessary for DNA replication to initiate. During S phase, dissociation of MCM from the chromatin prevents an or igin from firing more than once in a single cell cycle. The Cyclin-dep endent kinases (Cdks) provide an overall control of the cell cycle. In deed, Cdks have at least two important function in regulating DNA repl ication: Cdks both stimulate the initiation of DNA replication and pre vent replication to occur more than once in a single cell cycle. Altho ugh the details of these controls remain unclear, recent work indicate s that the interaction of the Cdks with Cdc6 and MCM proteins could re gulate their binding to the replication origins during the cell cycle.