Sci. Aging Knowl. Environ., 28 November 2001
Vol. 2001, Issue 9, p. or25

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ATR and ATRIP: Partners in Checkpoint Signaling

David Cortez, Saritha Guntuku, Jun Qin, and Stephen J. Elledge

http://sageke.sciencemag.org/cgi/content/abstract/sageke;2001/9/or25

Abstract: Science 294, 1713 (2001).

The checkpoint kinases ATM (ataxia telangiectasia mutated) and ATR (ATM- and Rad3-related) transduce genomic stress signals to halt cell cycle progression and promote DNA repair. We report the identification of an ATR-interacting protein (ATRIP) that is phosphorylated by ATR, regulates ATR expression, and is an essential component of the DNA damage checkpoint pathway. ATR and ATRIP both localize to intranuclear foci after DNA damage or inhibition of replication. Deletion of ATR mediated by the Cre recombinase caused the loss of ATR and ATRIP expression, loss of DNA damage checkpoint responses, and cell death. Therefore, ATR is essential for the viability of human somatic cells. Small interfering RNA directed against ATRIP caused the loss of both ATRIP and ATR expression and the loss of checkpoint responses to DNA damage. Thus, ATRIP and ATR are mutually dependent partners in cell cycle checkpoint signaling pathways.

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