Single Cell Analysis Reveals Multiple Requirements for Zinc in the Mammalian Cell Cycle | CU Experts

Abstract; ; Despite recognition of the fundamental role of zinc (Zn; 2+; ) for growth and proliferation, mechanisms of how Zn; 2+; deficiency arrests these processes remain enigmatic. We induced subtle intracellular Zn; 2+; perturbations and tracked asynchronously cycling cells throughout division using fluorescent reporters, high throughput microscopy, and quantitative analysis. We found that Zn; 2+; deficiency induces quiescence and Zn; 2+; resupply stimulates cell-cycle reentry. By monitoring single cells after Zn; 2+; deprivation, we found that depending on where cells were in the cell cycle, they either went quiescent or entered the cell cycle but stalled in S phase. Stalled cells were defective in DNA synthesis and had increased DNA damage levels, suggesting a role for Zn; 2+; in maintaining genome integrity. Finally, we found that Zn; 2+; deficiency-induced quiescence does not require the cell-cycle inhibitor p21. Overall, our study provides new insights into when Zn; 2+; is required during the mammalian cell cycle and the consequences Zn; 2+; deficiency.;

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