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Science 23 November 2001:
Vol. 294. no. 5547, pp. 1713 - 1716
DOI: 10.1126/science.1065521
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Reports

ATR and ATRIP: Partners in Checkpoint Signaling

David Cortez,12 Saritha Guntuku,12 Jun Qin,13 Stephen J. Elledge124*

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.

1 Verna and Mars McLean Department of Biochemistry and Molecular Biology,
2 Howard Hughes Medical Institute,
3 Department of Cell Biology,
4 Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
*   To whom correspondence should be addressed.

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Caffeine Inhibits Human Immunodeficiency Virus Type 1 Transduction of Nondividing Cells.
R. Daniel, E. Marusich, E. Argyris, R. Y. Zhao, A. M. Skalka, and R. J. Pomerantz (2005)
J. Virol. 79, 2058-2065
   Abstract »    Full Text »    PDF »
Filtering of Ineffective siRNAs and Improved siRNA Design Tool.
S. M. Yiu, P. W. H. Wong, T.W. Lam, Y.C. Mui, H. F. Kung, M. Lin, and Y. T. Cheung (2005)
Bioinformatics 21, 144-151
   Abstract »    Full Text »    PDF »
Ataxia Telangiectasia Mutated (ATM) and ATM and Rad3-related Protein Exhibit Selective Target Specificities in Response to Different Forms of DNA Damage.
C. E. Helt, W. A. Cliby, P. C. Keng, R. A. Bambara, and M. A. O'Reilly (2005)
J. Biol. Chem. 280, 1186-1192
   Abstract »    Full Text »    PDF »
Viral Transport of DNA Damage That Mimics a Stalled Replication Fork.
J. Jurvansuu, K. Raj, A. Stasiak, and P. Beard (2005)
J. Virol. 79, 569-580
   Abstract »    Full Text »    PDF »
G2 damage checkpoints: what is the turn-on?.
M. J. O'Connell and K. A. Cimprich (2005)
J. Cell Sci. 118, 1-6
   Abstract »    Full Text »    PDF »
Seckel syndrome exhibits cellular features demonstrating defects in the ATR-signalling pathway.
G. K. Alderton, H. Joenje, R. Varon, A. D. Borglum, P. A. Jeggo, and M. O'Driscoll (2004)
Hum. Mol. Genet. 13, 3127-3138
   Abstract »    Full Text »    PDF »
A Tel1/MRX-Dependent Checkpoint Inhibits the Metaphase-to-Anaphase Transition after UV Irradiation in the Absence of Mec1.
M. Clerici, V. Baldo, D. Mantiero, F. Lottersberger, G. Lucchini, and M. P. Longhese (2004)
Mol. Cell. Biol. 24, 10126-10144
   Abstract »    Full Text »    PDF »


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