Control of DNA replication by cyclin-dependent kinases in development.

Cyclin-dependent kinases (CDKs) are required for initiation of DNA replication in all eukaryotes, and appear to act at multiple levels to control replication origin firing, depending on the cell type and stage of development. In early development of many animals, both invertebrate and vertebrate, rapid cell cycling is coupled with transcriptional repression, and replication initiates at closely spaced replication origins with little or no sequence specificity. This organisation of DNA replication is modified during development as cell proliferation becomes more controlled and defined. In all eukaryotic cells, CDKs promote conversion of "licensed" pre-replication complexes (pre-RC) to active initiation complexes. In certain circumstances, CDKs may also control pre-RC formation, transcription of replication factor genes, chromatin remodelling, origin spacing, and organisation of replication origin clusters and replication foci within the nucleus. Although CDK1 and CDK2 have overlapping roles, there is a limit to their functional redundancy. Here, I review these findings and their implications for development.