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Global increase in replication fork speed during a p57KIP2-regulated erythroid cell fate switch
Yung Hwang1, Melinda Futran1, Daniel Hidalgo1
1Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Science Advances
|June 1, 2017
Summary
Cell cycle regulators control cell fate. Researchers found p57KIP2 slows DNA replication forks for progenitor self-renewal, a new role for cyclin-dependent kinase inhibitors in cell fate decisions.
Area of Science:
- Cell Biology
- Molecular Biology
- Developmental Biology
Background:
- Cell cycle regulators influence cell fate, including pluripotency and self-renewal.
- Mechanisms by which cell cycle regulators control cell fate are not well understood.
Purpose of the Study:
- Investigate the role of cell cycle regulation in cell fate decisions.
- Elucidate the mechanisms underlying an S phase-dependent cell fate switch in murine erythroid progenitors.
Main Methods:
- Studied in vivo transition of murine early erythroid progenitors from self-renewal to differentiation.
- Analyzed the role of p57KIP2 in regulating replication fork speed and S phase duration.
- Investigated the impact of p57KIP2 down-regulation on cell fate.
Main Results:
- Murine erythroid progenitors require p57KIP2-mediated slowing of replication forks for self-renewal.
- Differentiation involves rapid down-regulation of p57KIP2.
- p57KIP2 down-regulation leads to increased replication fork speed and a shorter S phase.
Conclusions:
- p57KIP2 has a novel function in regulating DNA replication dynamics for cell self-renewal.
- Specialized DNA replication dynamics are crucial for maintaining cell states and driving cell fate decisions.
- Cell cycle control of replication fork speed is integral to cell fate determination.
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