| Human embryonic stem cells are capable of executing G1/S checkpoint activation. | |
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MedLine Citation:
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PMID: 20518019 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Tomás Bárta; Vladimír Vinarský; Zuzana Holubcová; Dása Dolezalová; Jan Verner; Sárka Pospísilová; Petr Dvorák; Ales Hampl |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Stem cells (Dayton, Ohio) Volume: 28 ISSN: 1549-4918 ISO Abbreviation: Stem Cells Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-07-27 Completed Date: 2010-11-12 Revised Date: 2011-11-02 |
Medline Journal Info:
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Nlm Unique ID: 9304532 Medline TA: Stem Cells Country: United States |
Other Details:
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Languages: eng Pagination: 1143-52 Citation Subset: IM |
Affiliation:
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Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Cell Differentiation Cell Line Cyclin-Dependent Kinase 2 / metabolism DNA Damage G1 Phase* / radiation effects Humans Protein Kinases / metabolism Protein-Serine-Threonine Kinases / metabolism S Phase* / radiation effects Signal Transduction Stem Cells / cytology*, metabolism, radiation effects cdc25 Phosphatases / metabolism |
| Chemical | |
Reg. No./Substance:
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EC 2.7.-/Protein Kinases; EC 2.7.1.11/checkpoint kinase 2; EC 2.7.1.37/CDK2 protein, human; EC 2.7.11.1/Checkpoint kinase 1; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.22/Cyclin-Dependent Kinase 2; EC 3.1.3.48/CDC25A protein, human; EC 3.1.3.48/cdc25 Phosphatases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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