Where the cell cycle and histones meet
- Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA
This extract was created in the absence of an abstract.
Since the discovery of mammalian cyclin E and the D-type 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.
Cyclins and CDKs
The cell cycle is the process through which cells duplicate themselves. The holistic view of the cell cycle of decades ago predicts that this duplication must involve not only synthesis of a copy of the genetic material but a doubling of the ancillary components of the genome and the cell's biomass (Mitchison 1971). The discovery of the key cell cycle regulatory elements, the cyclins and CDKs, has allowed us to understand how initiation of DNA synthesis is controlled. How the other processes of cellular duplication are regulated remains elusive.
The principle CDKs responsible for G1 progression and entrance into S phase are CDK2, CDK3, CDK4, and CDK6. The D-type cyclins (D1, D2, and D3) are the regulatory …
