Document Detail


The multiple checkpoint functions of CHK1 and CHK2 in maintenance of genome stability.
MedLine Citation:
PMID:  18508566     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cell cycle checkpoints are pivotal mechanisms safeguarding genome stability. Cells that harbor defects in checkpoints are predisposed to genome instability and neoplastic transformation. Two structurally-unrelated protein kinases, CHK1 and CHK2, are implicated in several major checkpoints of the cell cycle, providing a crucial linkage between the upstream sensors of the checkpoints and the cell cycle engine. Variations of the ATM/ATR-CHK1/CHK2-CDC25-CDK axis underlie the molecular basis of the replication checkpoint, the intra-S phase checkpoint, and the G2 DNA damage checkpoint. Although some aspects of the pathway remain contentious, the ATM/ATR-CHK1/CHK2-p53-p21CIP1/WAF1-CDK axis is believed to play an important role in the G1 DNA damage checkpoint. Recent data also reveal that CHK1 may play a role in the spindle-assembly checkpoint. Finally, CHK1 and CHK2 are implicated in linking the cell cycle to diverse processes such as senescence and the circadian cycle. In this review article, we provide an overview of how the multi-tasking nature of CHK1 and CHK2 is achieved in vertebrate cells.
Authors:
Yue Chen; Randy Y C Poon
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review     Date:  2008-05-01
Journal Detail:
Title:  Frontiers in bioscience : a journal and virtual library     Volume:  13     ISSN:  1093-4715     ISO Abbreviation:  Front. Biosci.     Publication Date:  2008  
Date Detail:
Created Date:  2008-05-29     Completed Date:  2008-09-19     Revised Date:  2011-11-02    
Medline Journal Info:
Nlm Unique ID:  9709506     Medline TA:  Front Biosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5016-29     Citation Subset:  IM    
Affiliation:
Department of Biochemistry, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong.
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MeSH Terms
Descriptor/Qualifier:
Cell Cycle
DNA Damage
DNA Replication
Genomic Instability / genetics*
Humans
Protein Kinases / genetics*
Protein-Serine-Threonine Kinases / genetics*
S Phase / genetics
Chemical
Reg. No./Substance:
EC 2.7.-/Protein Kinases; EC 2.7.1.11/checkpoint kinase 2; EC 2.7.11.1/Checkpoint kinase 1; 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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