Fig. 8. Model for positive and negative regulatory roles of cyclin E–Cdk2 and MCM5 during DNA and centrosome replication. A positive role for cyclin E–Cdk2 is indicated by the arrowhead, e.g. phosphorylation of Cdc45 to initiate origin firing during DNA replication or of nucleophosmin B to initiate centrosome duplication. The inhibitory arm denotes the role of cyclin E–Cdk2 in preventing re-replication of DNA or centrosomes in the same cycle (e.g. by preventing re-loading of MCM proteins onto origins of replication on DNA or recruiting MCM5 to centrosomes).