Deciding when to exit

Abstract

A new imaging approach can distinguish between cells destined to stop proliferating and those committed to re-entering the cell cycle in live animals.

Keywords: C. elegans; cdk sensor; cell biology; cell cycle; cell proliferation; developmental biology; g1/g0; quiescence; zebrafish.

Figure 1.. Monitoring cell cycle progression using a fluorescent biosensor.

(A) As cells grow and prepare to divide they pass through four different phases of the cell cycle: G1, S, G2, M. During the course of this cycle, the activity of cyclin-dependent kinases (CDKs) changes. These fluctuations in activity can be monitored using a fluorescent reporter protein that contains a portion of human DNA helicase B (DHB), which moves from the nucleus to the cytoplasm when phosphorylated by active CDKs. Thus, changes in the levels of DHB in the nucleus and cytoplasm (depicted in shades of orange/red) can be used to determine a cell’s CDK activity. At the start of G1, CDK activity is low and DHB remains in the nucleus (shown in red). Some G1 cells maintain this low level of activity (CDK^low) and exit the cell cycle to become quiescent, while cells with increasing levels of CDK activity (CDK^inc) commit to another cell cycle and enter S-phase. (B) Adikes et al. showed that the DHB reporter could monitor cell cycle progression of individual cells in live animals, such as the embryo of a zebrafish. It can also identify which cells have exited the cell cycle and which are preparing for division.