Transient Zn 2+ deficiency induces replication stress and compromises daughter cell proliferation.

Zinc is an essential micronutrient required for cells to grow and proliferate. However, the mechanism of how zinc influences proliferation is unknown. We show that short exposure to mild zinc deficiency in S-phase impairs DNA synthesis and induces replication stress, leading to pauses in daughter cell proliferation. However, pulses of low zinc during other phases of the cell cycle don't affect mother cell cycle progression or daughter cell proliferation. These results indicate that while zinc is important for many proteins, during the cell cycle short pulses of mild zinc deficiency have the biggest impact on a cell's ability to synthesize DNA, suggesting that DNA polymerase complex acts as a gate keeper, sensing zinc status in the cell.