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DNA Repair (Amst). 2004 Aug-Sep;3(8-9):901-8.

Regulation of DNA replication by ATR: signaling in response to DNA intermediates.

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Department of Genetics and Development, Hammer Health Sciences Center, Room 1620, Columbia University College of Physicians and Surgeons, 701 W. 168th Street, New York, NY 10032, USA.


The nuclear protein kinase ATR controls S-phase progression in response to DNA damage and replication fork stalling, including damage caused by ultraviolet irradiation, hyperoxia, and replication inhibitors like aphidicolin and hydroxyurea. ATR activation and substrate specificity require the presence of adapter and mediator molecules, ultimately resulting in the downstream inhibition of the S-phase kinases that function to initiate DNA replication at origins of replication. The data reviewed strongly support the hypothesis that ATR is activated in response to persistent RPA-bound single-stranded DNA, a common intermediate of unstressed and damaged DNA replication and metabolism.

[Indexed for MEDLINE]

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