Studying the cell cycle, without the cell!

The 2001 Nobel Prize in Medicine went to Lee Hartwell, Tim Hunt, and Paul Nurse for their elucidation of the mechanisms underlying cell cycle control. It may be surprising, then, that many of the studies that led to these discoveries were performed in the absence of cells. Such a study was performed in this 1987 study by Christopher Hutchison and colleagues, using cell free extracts of Xenopus eggs. Incredibly, these cytoplasmic extracts were able to generate pronuclei derived from sperm heads, allowing researchers to employ pulse and continuous labelling to examine DNA synthesis. By performing these experiments in the presence and absence of a protein synthesis inhibitor, the authors of this study were able to determine that DNA synthesis is cyclic, thus laying the foundation for some of Tim Hunt’s work. 

Our understanding of the cell cycle in 1989 (Murray and Kirschner, 1989)

• The paper. 

Building on this, Tim Hunt's group used cell-free extracts to show that transcription of cyclins were necessary for entry into mitosis. All of this is summarised in this 1989 review by Andrew Murray and Marc Kirschner.