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An overactivated ATR/CHK1 pathway is responsible for the prolonged G2 accumulation in irradiated AT cellsInduction 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.
Document ID
20040087659
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
External Source(s)
Authors
Wang, Xiang
(Kimmel Cancer Center of Jefferson Medical College, Thomas Jefferson University Philadelphia, Pennsylvania 19107, United States)
Khadpe, Jay
Hu, Baocheng
Iliakis, George
Wang, Ya
Date Acquired
August 21, 2013
Publication Date
August 15, 2003
Publication Information
Publication: The Journal of biological chemistry
Volume: 278
Issue: 33
ISSN: 0021-9258
Subject Category
Life Sciences (General)
Funding Number(s)
CONTRACT_GRANT: R25 CA48010
CONTRACT_GRANT: CA76203
CONTRACT_GRANT: CA42026
CONTRACT_GRANT: P30-CA56036
CONTRACT_GRANT: CA56706
Distribution Limits
Public
Copyright
Other
Keywords
NASA Discipline Radiation Health
Non-NASA Center
NASA Program Biomedical Research and Countermeasures

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