Where the cell cycle and histones meet: Figure 1.

Since the discovery of mammalian cyclin E and the Dtype cyclins in 1991, much effort has been devoted towards elucidating their role in G1 progression and S phase entry. Key to this endeavor has been the identification and characterization of substrates for cyclin E–CDK2 and D-type cyclin–CDK4 and cyclin–CDK6 complexes. Whereas there appears to be only one critical substrate of CDK4 and CDK6, the list of CDK2 substrates continues to lengthen in line with the realization that the principal mediators of cyclin E–CDK2 action are yet to be identified. The papers by Ma et al. and Zhao et al. in this issue bring a new dimension to our understanding of cyclin E–CDK2, by showing that NPAT, a previously identified CDK2 substrate, links the cell cycle to histone gene transcription. This provides us with the beginnings of how the action of CDKs is linked to the periodic synthesis of histones in mammalian cells. These works illuminate our picture of how the cell cycle control elements may influence multiple biosynthetic processes as integral to S phase as duplication of the genetic material itself.