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Updated: Jun 26, 2026
Avidity-based Extracellular Interaction Screening (AVEXIS) for the Scalable Detection of Low-affinity Extracellular Receptor-Ligand Interactions
Published on: March 5, 2012
ATR and ATRIP: partners in checkpoint signaling
1Verna and Mars McLean Department of Biochemistry and Molecular Biology, Howard Hughes Medical Institute, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
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.
Insights
Researchers identified ATR-interacting protein (ATRIP), crucial for the DNA damage checkpoint. ATRIP and ATR are essential, mutually dependent partners in cell cycle signaling and DNA repair.
Area of Science:
- Cellular biology
- Molecular biology
- Genetics
Background:
- Checkpoint kinases ATM and ATR regulate cell cycle progression and DNA repair in response to genomic stress.
- The DNA damage checkpoint pathway is critical for maintaining genomic stability.
Purpose of the Study:
- To identify and characterize novel components of the DNA damage checkpoint pathway.
- To elucidate the functional relationship between ATR and its interacting proteins.
Main Methods:
- Identification of ATR-interacting protein (ATRIP) through biochemical assays.
- Analysis of ATRIP phosphorylation by ATR.
- Investigation of ATR and ATRIP expression and localization using immunofluorescence.
- Assessment of DNA damage checkpoint responses following ATR or ATRIP depletion via Cre-mediated deletion or small interfering RNA (siRNA).
Main Results:
- ATRIP is phosphorylated by ATR and regulates ATR expression.
- ATR and ATRIP colocalize to intranuclear foci upon DNA damage or replication inhibition.
- ATR deletion leads to loss of ATRIP expression, checkpoint failure, and cell death, confirming ATR's essential role in human somatic cells.
- ATRIP depletion results in the loss of both ATRIP and ATR expression and abrogates DNA damage checkpoint responses.
Conclusions:
- ATRIP is an essential component of the DNA damage checkpoint pathway.
- ATR and ATRIP function as mutually dependent partners in cell cycle checkpoint signaling.
- The ATR-ATRIP complex is vital for maintaining genomic integrity and cell viability.
