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

View ORCID ProfileMaria N. Lo, View ORCID ProfileLeah J. Damon, Jian Wei Tay, View ORCID ProfileAmy E. Palmer
doi: https://doi.org/10.1101/735134
Maria N. Lo
1Department of Biochemistry and BioFrontiers Institute, University of Colorado Boulder, Boulder CO 80303
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Leah J. Damon
1Department of Biochemistry and BioFrontiers Institute, University of Colorado Boulder, Boulder CO 80303
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Jian Wei Tay
1Department of Biochemistry and BioFrontiers Institute, University of Colorado Boulder, Boulder CO 80303
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Amy E. Palmer
1Department of Biochemistry and BioFrontiers Institute, University of Colorado Boulder, Boulder CO 80303
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  • For correspondence: amy.palmer@colorado.edu
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Abstract

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.

Footnotes

  • https://biof-git.colorado.edu/biofrontiers-imaging/palmer-zinc-cell-cycle

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted August 14, 2019.
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Single Cell Analysis Reveals Multiple Requirements for Zinc in the Mammalian Cell Cycle
Maria N. Lo, Leah J. Damon, Jian Wei Tay, Amy E. Palmer
bioRxiv 735134; doi: https://doi.org/10.1101/735134
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Single Cell Analysis Reveals Multiple Requirements for Zinc in the Mammalian Cell Cycle
Maria N. Lo, Leah J. Damon, Jian Wei Tay, Amy E. Palmer
bioRxiv 735134; doi: https://doi.org/10.1101/735134

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