Document Detail

Exposure to acute hypoxia induces a transient DNA damage response which includes Chk1 and TLK1.
MedLine Citation:
PMID:  20581459     Owner:  NLM     Status:  MEDLINE    
Severe hypoxia has been demonstrated to induce a replication arrest which is associated with decreased levels of nucleotides. Chk1 is rapidly phosphorylated in response to severe hypoxia and in turn deactivates TLK1 through phosphorylation. Loss of Chk1 has been shown to sensitize cells to hypoxia/reoxygenation. After short (acute) exposure to hypoxia this is due to an increased rate of reoxygenation-induced replication restart and subsequent p53-dependent apoptosis. After longer (chronic) exposure to hypoxia S phase cells do not undergo reoxygenation-induced replication restart. Cells exposed to these levels of hypoxia however are sensitive to loss of Chk1. This suggests a new role for Chk1 in the cell cycle response to reoxygenation.
Isabel M Pires; Zuzana Bencokova; Chris McGurk; Ester M Hammond
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cell cycle (Georgetown, Tex.)     Volume:  9     ISSN:  1551-4005     ISO Abbreviation:  Cell Cycle     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2011-04-18     Completed Date:  2011-06-15     Revised Date:  2012-09-18    
Medline Journal Info:
Nlm Unique ID:  101137841     Medline TA:  Cell Cycle     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2502-7     Citation Subset:  IM    
Copyright Information:
© 2010 Landes Bioscience
The Gray Institute for Radiation Oncology and Biology, University of Oxford, Oxford, UK.
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MeSH Terms
Cell Hypoxia / drug effects
DNA Damage*
DNA Repair / drug effects
DNA Replication / drug effects
Models, Biological
Oxygen / pharmacology
Phosphorylation / drug effects
Protein Kinases / metabolism*
Protein-Serine-Threonine Kinases / metabolism*
Rad51 Recombinase / metabolism
Signal Transduction / drug effects
Grant Support
C6515/A9321//Cancer Research UK
Reg. No./Substance:
7782-44-7/Oxygen; EC 2.7.-/Protein Kinases; EC kinase 1; EC Kinases; EC 2.7.7.-/Rad51 Recombinase

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