An ATM-independent S-phase checkpoint response involves CHK1 pathway

After exposure to genotoxic stress, proliferating cells actively slow down the DNA replication through a S-phase checkpoint to provide time for repair. We report that in addition to the ataxia-telangiectasia mutated (ATM)-dependent pathway that controls the fast response, there is an ATM-independent...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2002-03, Vol.62 (6), p.1598-1603
Main Authors: Zhou, Xiang-Yang, Wang, Xiang, Hu, Baocheng, Guan, Jun, Iliakis, George, Wang, Ya
Format: Article
Language:English
Subjects:
Ataxia Telangiectasia - pathology
Ataxia Telangiectasia Mutated Proteins
CDC2-CDC28 Kinases
Cell Cycle Proteins
Checkpoint Kinase 1
Cyclin-Dependent Kinase 2
Cyclin-Dependent Kinases - antagonists & inhibitors
Cyclin-Dependent Kinases - metabolism
DNA - biosynthesis
DNA Replication - drug effects
DNA Replication - radiation effects
DNA-Binding Proteins
Enzyme Activation
Fibroblasts - cytology
Fibroblasts - drug effects
Fibroblasts - enzymology
Fibroblasts - radiation effects
Humans
Life Sciences (General)
Oligonucleotides, Antisense - genetics
Oligonucleotides, Antisense - pharmacology
Protein Kinases - genetics
Protein Kinases - metabolism
Protein-Serine-Threonine Kinases - antagonists & inhibitors
Protein-Serine-Threonine Kinases - genetics
Protein-Serine-Threonine Kinases - metabolism
Protein-Serine-Threonine Kinases - physiology
S Phase - drug effects
S Phase - physiology
S Phase - radiation effects
Space life sciences
Tumor Suppressor Proteins
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Summary:After exposure to genotoxic stress, proliferating cells actively slow down the DNA replication through a S-phase checkpoint to provide time for repair. We report that in addition to the ataxia-telangiectasia mutated (ATM)-dependent pathway that controls the fast response, there is an ATM-independent pathway that controls the slow response to regulate the S-phase checkpoint after ionizing radiation in mammalian cells. The slow response of S-phase checkpoint, which is resistant to wortmannin, sensitive to caffeine and UCN-01, and related to cyclin-dependent kinase phosphorylation, is much stronger in CHK1 overexpressed cells, and it could be abolished by Chk1 antisense oligonucleotides. These results provide evidence that the ATM-independent slow response of S-phase checkpoint involves CHK1 pathway.
ISSN:0008-5472