Cited by 993DNA Repair MechanismsCancer-related Molecular PathwaysGenomics and Chromatin Dynamics

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ATR and ATRIP: Partners in Checkpoint Signaling

Cortez, David, Guntuku, Saritha, Qin, Jun, Elledge, Stephen J.·2001·Science

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Abstract

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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Authors: Cortez, D., Guntuku, S., Qin, J., & Elledge, S. J.
Affiliations: Howard Hughes Medical Institute (US)
Verna and Mars McLean Department of Biochemistry and Molecular Biology,
Corresponding author: Elledge, Stephen J.
ORCID: Cortez, David
Elledge, Stephen J.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2001-11-23
Volume: 294
Issue: 5547
Pages: 1713-1716
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.1065521
OpenAlex: W1968552183
Cited by: 985
References: 20
Citations by year: 2026: 23 · 2025: 23 · 2024: 28 · 2023: 35 · 2022: 23 · 2021: 37 · 2020: 29 · 2019: 29 · 2018: 31 · 2017: 27 · 2016: 39 · 2015: 38 · 2014: 41 · 2013: 52 · 2012: 38
FWCI: 16.99
Type: journal article
Language: en
Open access: closed
Locations: Science (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords: ATR, ATRIP, ATM, DNA damage checkpoint, genomic stress, cell cycle arrest, DNA repair, replication stress, protein phosphorylation, cell viability
MeSH terms: Amino Acid Sequence, Animals, Cell Cycle, Cell Line, Cell Survival, DNA Damage, DNA-Binding Proteins, Exodeoxyribonucleases, Exons, HeLa Cells, Humans, Molecular Sequence Data, Molecular Weight, Phosphoproteins, Phosphorylation, Precipitin Tests, Protein Binding, Viral Proteins, Signal Transduction, Sequence Alignment, Cell Death, Conserved Sequence, Protein Serine-Threonine Kinases, Gene Deletion, Cell Cycle Proteins, Integrases, Genes, Essential, Adaptor Proteins, Signal Transducing, Ataxia Telangiectasia Mutated Proteins

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ATR and ATRIP: Partners in Checkpoint Signaling

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