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Embryonic Stem Cells/Induced Pluripotent Stem Cells
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Human Embryonic Stem Cells Are Capable of Executing G1/S Checkpoint Activation†‡§
Article first published online: 1 JUN 2010
DOI: 10.1002/stem.451
Copyright © 2010 AlphaMed Press
Additional Information
How to Cite
Bárta, T., Vinarský, V., Holubcová, Z., Doležalová, D., Verner, J., Pospíšilová, Š., Dvořák, P. and Hampl, A. (2010), Human Embryonic Stem Cells Are Capable of Executing G1/S Checkpoint Activation. STEM CELLS, 28: 1143–1152. doi: 10.1002/stem.451
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Author contributions: T.B.: conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing; V.V.: collection and assembly of data; Z.H.: collection and assembly of data; D.D.: collection and assembly of data; J.V.: collection and assembly of data; Š.P.: data analysis and interpretation; P.D.: data analysis and interpretation; A.H.: conception and design, data analysis and interpretation, manuscript writing, final approval of manuscript.
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First published online in STEM CELLS EXPRESS June 1, 2010; available online without subscription through the open access option.
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Disclosure of potential conflicts of interest is found at the end of this article.
Publication History
- Issue published online: 20 JUL 2010
- Article first published online: 1 JUN 2010
- Manuscript Accepted: 13 MAY 2010
- Manuscript Received: 8 MAR 2010
Funded by
- Ministry of Education, Youth, and Sports of the Czech Republic. Grant Numbers: MSM0021622430, MUNI/E/0118/2009, 1M0538
- Academy of Sciences of the Czech Republic. Grant Numbers: AV0Z50390512, AV0Z50390703
- EU. Grant Number: LSHGCT-2006-018739
- Ministry of Health of the Czech Republic. Grant Number: IGA MZ CR NS10439-3/2009
Keywords:
- Human embryonic stem cells;
- DNA damage;
- Checkpoint activation;
- UVC;
- Cdc25A;
- p53
Abstract
Embryonic stem cells progress very rapidly through the cell cycle, allowing limited time for cell cycle regulatory circuits that typically function in somatic cells. Mechanisms that inhibit cell cycle progression upon DNA damage are of particular importance, as their malfunction may contribute to the genetic instability observed in human embryonic stem cells (hESCs). In this study, we exposed undifferentiated hESCs to DNA-damaging ultraviolet radiation-C range (UVC) light and examined their progression through the G1/S transition. We show that hESCs irradiated in G1 phase undergo cell cycle arrest before DNA synthesis and exhibit decreased cyclin-dependent kinase two (CDK2) activity. We also show that the phosphatase Cdc25A, which directly activates CDK2, is downregulated in irradiated hESCs through the action of the checkpoint kinases Chk1 and/or Chk2. Importantly, the classical effector of the p53-mediated pathway, protein p21, is not a regulator of G1/S progression in hESCs. Taken together, our data demonstrate that cultured undifferentiated hESCs are capable of preventing entry into S-phase by activating the G1/S checkpoint upon damage to their genetic complement. STEM CELLS 2010;28:1143–1152