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

Zhou, Xiang-Yang; Wang, Xiang; Hu, Baocheng; Guan, Jun; Iliakis, George; Wang, Ya

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NASA NTRS · 20040088401

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

Zhou, Xiang-Yang·Wang, Xiang·Hu, Baocheng·Guan, Jun·Iliakis, George·Wang, Ya

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Abstract

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.

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Non-NASA Center NASA Discipline Radiation Health Protein-Serine-Threonine Kinases/antagonists & inhibitors/genetics/metabolism CDC2-CDC28 Kinases S Phase/drug effects/physiology/radiation effects Human DNA Replication/drug effects/radiation effects Ataxia Telangiectasia/pathology Enzyme Activation Protein Kinases/genetics/metabolism DNA/biosynthesis Oligonucleotides, Antisense/genetics/pharmacology Fibroblasts/cytology/drug effects/enzymology/radiation effects Cyclin-Dependent Kinases/antagonists & inhibitors/metabolism Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S

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Zhou, Xiang-Yang, Wang, Xiang, Hu, Baocheng, Guan, Jun, Iliakis, George, Wang, Ya. 2002-03-15. An ATM-independent S-phase checkpoint response involves CHK1 pathway. https://ntrs.nasa.gov/citations/20040088401

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