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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
33
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pubmed:dateCreated |
2003-8-11
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pubmed:abstractText |
Induction of checkpoint responses in G1, S, and G2 phases of the cell cycle after exposure of cells to ionizing radiation (IR) is essential for maintaining genomic integrity. Ataxia telangiectasia mutated (ATM) plays a key role in initiating this response in all three phases of the cell cycle. However, cells lacking functional ATM exhibit a prolonged G2 arrest after IR, suggesting regulation by an ATM-independent checkpoint response. The mechanism for this ataxia telangiectasia (AT)-independent G2-checkpoint response remains unknown. We report here that the G2 checkpoint in irradiated human AT cells derives from an overactivation of the ATR/CHK1 pathway. Chk1 small interfering RNA abolishes the IR-induced prolonged G2 checkpoint and radiosensitizes AT cells to killing. These results link the activation of ATR/CHK1 with the prolonged G2 arrest in AT cells and show that activation of this G2 checkpoint contributes to the survival of AT cells.
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pubmed:grant |
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pubmed:keyword |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/7-hydroxystaurosporine,
http://linkedlifedata.com/resource/pubmed/chemical/ATR protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Alkaloids,
http://linkedlifedata.com/resource/pubmed/chemical/Caffeine,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Checkpoint kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphodiesterase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Staurosporine
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
278
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
30869-74
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pubmed:dateRevised |
2011-11-2
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pubmed:meshHeading |
pubmed-meshheading:12791699-Alkaloids,
pubmed-meshheading:12791699-Caffeine,
pubmed-meshheading:12791699-Cell Cycle Proteins,
pubmed-meshheading:12791699-Cell Line, Transformed,
pubmed-meshheading:12791699-Cell Survival,
pubmed-meshheading:12791699-Enzyme Inhibitors,
pubmed-meshheading:12791699-Fibroblasts,
pubmed-meshheading:12791699-G2 Phase,
pubmed-meshheading:12791699-Humans,
pubmed-meshheading:12791699-Phosphodiesterase Inhibitors,
pubmed-meshheading:12791699-Protein Kinase Inhibitors,
pubmed-meshheading:12791699-Protein Kinases,
pubmed-meshheading:12791699-Protein-Serine-Threonine Kinases,
pubmed-meshheading:12791699-RNA, Small Interfering,
pubmed-meshheading:12791699-Radiation, Ionizing,
pubmed-meshheading:12791699-Staurosporine
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pubmed:year |
2003
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pubmed:articleTitle |
An overactivated ATR/CHK1 pathway is responsible for the prolonged G2 accumulation in irradiated AT cells.
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pubmed:affiliation |
Department of Radiation Oncology, Kimmel Cancer Center of Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.
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