| Chk2/Cds1 protein kinase blocks apoptosis during early development of Xenopus laevis. | |
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MedLine Citation:
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PMID: 15937936 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Early Xenopus laevis embryos possess cell cycles that do not arrest at checkpoints in response to damaged DNA. At the midblastula transition (MBT), embryos with damaged DNA undergo apoptosis. After the MBT, DNA damage triggers cell cycle arrest rather than apoptosis. The transition from checkpoint-unregulated to checkpoint-regulated cycles makes Xenopus embryos compelling for studying mechanisms regulating response to genomic damage. The DNA damage checkpoint is mediated by the Chk2/Cds1 kinase. Conflicting evidence implicates Chk2 as an inhibitor or promoter of apoptosis. To better understand the developmental function of Chk2, we expressed wild-type (wt) and dominant-negative (DN) Chk2 in Xenopus embryos. Wt-Chk2 created a pre-MBT checkpoint due to degradation of Cdc25A and phosphorylation of cyclin-dependent kinases. Embryos expressing DN-Chk2 developed normally until gastrulation and then underwent apoptosis. Conversely, low doses of wt-Chk2 blocked radiation-induced apoptosis. Therefore, Chk2 operates at a switch between cell cycle arrest or apoptosis in response to genomic assaults. |
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Authors:
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Brian N Wroble; Jill C Sible |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Developmental dynamics : an official publication of the American Association of Anatomists Volume: 233 ISSN: 1058-8388 ISO Abbreviation: Dev. Dyn. Publication Date: 2005 Aug |
Date Detail:
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Created Date: 2005-07-21 Completed Date: 2005-12-02 Revised Date: 2011-11-02 |
Medline Journal Info:
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Nlm Unique ID: 9201927 Medline TA: Dev Dyn Country: United States |
Other Details:
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Languages: eng Pagination: 1359-65 Citation Subset: IM |
Copyright Information:
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(c) 2005 Wiley-Liss, Inc. |
Affiliation:
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Department of Biology, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061-0406, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis / physiology*, radiation effects Blastula / enzymology*, radiation effects Cell Cycle / physiology, radiation effects Protein-Serine-Threonine Kinases / genetics, physiology*, radiation effects X-Rays Xenopus Proteins / genetics, physiology*, radiation effects Xenopus laevis |
| Grant Support | |
ID/Acronym/Agency:
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R01 GM59688/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Xenopus Proteins; EC 2.7.1.11/checkpoint kinase 2; EC 2.7.11.1/Protein-Serine-Threonine Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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