Document Detail


Chk2/Cds1 protein kinase blocks apoptosis during early development of Xenopus laevis.
MedLine Citation:
PMID:  15937936     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Brian N Wroble; Jill C Sible
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
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:
Created Date:  2005-07-21     Completed Date:  2005-12-02     Revised Date:  2011-11-02    
Medline Journal Info:
Nlm Unique ID:  9201927     Medline TA:  Dev Dyn     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1359-65     Citation Subset:  IM    
Copyright Information:
(c) 2005 Wiley-Liss, Inc.
Affiliation:
Department of Biology, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061-0406, USA.
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MeSH Terms
Descriptor/Qualifier:
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:
R01 GM59688/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Xenopus Proteins; EC 2.7.1.11/checkpoint kinase 2; EC 2.7.11.1/Protein-Serine-Threonine Kinases

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