Single cell analysis reveals multiple requirements for zinc in the mammalian cell cycle

For an animal to grow, its cells have to divide. Cell division can only take place if the cell meets certain conditions: for example, the cell’s DNA must not be damaged. To ensure that cells only divide when these conditions are met, the cell goes through a series of stages or phases with checkpoints known as the cell cycle. The ability to control whether cells divide is essential for an animal to correctly form organs and tissues, or to heal wounds. Zinc is a metal that animals get in their diet, and when zinc levels are low, animals usually grow more slowly because their cells stop dividing. Around 2 billion people worldwide do not get enough zinc in their diet. Amongst other processes, zinc is necessary for DNA repair, which could explain why low levels of zinc stop the cell from dividing. However, the evidence for why zinc is required for cell division is contradictory. Although it seems clear that zinc is necessary for cells to progress through the cell cycle, it was unknown whether it is needed at a specific stage or whether it influences a cell’s decision to divide. Lo et al. have used microscopy to examine the effects that different levels of zinc had on individual cells grown in the lab. The results suggest that cells can monitor the levels of zinc in their environment, and respond to low levels by shutting down growth and cell division. This happens independently of the stage of the cell cycle a cell finds itself in, explaining the discrepancies between older studies. Additionally, the results show that although zinc is required for DNA repair, this process is not what triggers cells to stop dividing in the absence of zinc. In fact, low levels of zinc seem to be stopping cell division through a previously unknown mechanism. Lo et al.’s findings illustrate the high sensitivity of cells to changes in zinc availability and highlight the importance of zinc in our diet. Further study of how cells determine zinc levels and how those levels affect the cell cycle may help explain zinc’s role in health and disease.