RT Journal Article
SR Electronic
T1 Single Cell Analysis Reveals Multiple Requirements for Zinc in the Mammalian Cell Cycle
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 735134
DO 10.1101/735134
A1 Maria N. Lo
A1 Leah J. Damon
A1 Jian Wei Tay
A1 Amy E. Palmer
YR 2019
UL http://biorxiv.org/content/early/2019/08/14/735134.abstract
AB Despite recognition of the fundamental role of zinc (Zn2+) for growth and proliferation, mechanisms of how Zn2+ deficiency arrests these processes remain enigmatic. We induced subtle intracellular Zn2+ perturbations and tracked asynchronously cycling cells throughout division using fluorescent reporters, high throughput microscopy, and quantitative analysis. We found that Zn2+ deficiency induces quiescence and Zn2+ resupply stimulates cell-cycle reentry. By monitoring single cells after Zn2+ 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 Zn2+ in maintaining genome integrity. Finally, we found that Zn2+ deficiency-induced quiescence does not require the cell-cycle inhibitor p21. Overall, our study provides new insights into when Zn2+ is required during the mammalian cell cycle and the consequences Zn2+ deficiency.