| Title: |
Global increase in replication fork speed during a p57KIP2-regulated erythroid cell fate switch |
| Authors: |
Hwang, Yung; Futran, Melinda; Hidalgo, Daniel; Pop, Ramona; Iyer, Divya Ramalingam; Scully, Ralph; Rhind, Nicholas; Socolovsky, Merav |
| Contributors: |
Department of Biochemistry and Molecular Pharmacology; Department of Molecular, Cell and Cancer Biology |
| Source: |
Science advances ; 3 ; 5 ; e1700298 |
| Publication Year: |
2022 |
| Collection: |
University of Massachusetts, Medical School: eScholarship@UMMS |
| Subject Terms: |
CDK inhibitors; cell cycle; cell fate decision; differentiation; erythropoiesis; hematopoiesis; replication; self renewal; Cell Biology; Cellular and Molecular Physiology; Developmental Biology; Molecular Biology |
| Description: |
Cell cycle regulators are increasingly implicated in cell fate decisions, such as the acquisition or loss of pluripotency and self-renewal potential. The cell cycle mechanisms that regulate these cell fate decisions are largely unknown. We studied an S phase-dependent cell fate switch, in which murine early erythroid progenitors transition in vivo from a self-renewal state into a phase of active erythroid gene transcription and concurrent maturational cell divisions. We found that progenitors are dependent on p57KIP2-mediated slowing of replication forks for self-renewal, a novel function for cyclin-dependent kinase inhibitors. The switch to differentiation entails rapid down-regulation of p57KIP2 with a consequent global increase in replication fork speed and an abruptly shorter S phase. Our work suggests that cell cycles with specialized global DNA replication dynamics are integral to the maintenance of specific cell states and to cell fate decisions. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
Link to Article in PubMed; Sci Adv. 2017 May 26;3(5):e1700298. doi:10.1126/sciadv.1700298. eCollection 2017 May. Link to article on publisher's site; http://hdl.handle.net/20.500.14038/40354; https://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=4160&context=oapubs&unstamped=1; https://escholarship.umassmed.edu/oapubs/3152; oapubs/3152 |
| DOI: |
10.1126/sciadv.1700298 |
| Availability: |
https://doi.org/10.1126/sciadv.1700298; https://hdl.handle.net/20.500.14038/40354; https://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=4160&context=oapubs&unstamped=1; https://escholarship.umassmed.edu/oapubs/3152 |
| Accession Number: |
edsbas.1B19EEBA |
| Database: |
BASE |