ArticleThe Journal of biological chemistry
ATR activation is regulated by dimerization of ATR activating proteins.
Article in The Journal of biological chemistry. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- Comprehensive analysis of regulated cell death pathways: intrinsic disorder, protein-protein interactions, and cross-pathway communication.Apoptosis : an international journal on programmed cell death · 2025Pooled it
- An updated view on lagging strand DNA replication: implications for the replication stress response.Cell cycle (Georgetown, Tex.) · 2026Article
- Dpb11 facilitates the colocalization of Mec1-Ddc2 with its activators on gapped DNA.Cell reports · 2026Article
- Molecular interplay between the DNA damage checkpoint kinase Mec1-Ddc2 and its activator Dpb11 on gapped DNA.bioRxiv : the preprint server for biology · 2025Article
- Protein Phosphatase 2ACα Regulates ATR-Mediated Endogenous DNA Damage Response Against Microcephaly.Molecular neurobiology · 2025Article
- The Potential for Targeting GCancers · 2024Review
- Targeting ATR Pathway in Solid Tumors: Evidence of Improving Therapeutic Outcomes.International journal of molecular sciences · 2024Review
- NRF2 promotes radiation resistance by cooperating with TOPBP1 to activate the ATR-CHK1 signaling pathway.Theranostics · 2024Article
- Key molecular DNA damage responses of human cells to radiation.Frontiers in cell and developmental biology · 2024Review
- Structural characterization of human RPA70N association with DNA damage response proteins.eLife · 2023Article
- Review
- Targeting Replication Stress Response Pathways to Enhance Genotoxic Chemo- and Radiotherapy.Molecules (Basel, Switzerland) · 2022Review
- Article
- The Potential Important Role of Mitochondrial Rieske Iron-Sulfur Protein as a Novel Therapeutic Target for Pulmonary Hypertension in Chronic Obstructive Pulmonary Disease.Biomedicines · 2022Review
- MRN-dependent and independent pathways for recruitment of TOPBP1 to DNA double-strand breaks.PloS one · 2022Article
- DNA damage responses that enhance resilience to replication stress.Cellular and molecular life sciences : CMLS · 2021Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The checkpoint kinase ATR regulates DNA repair, cell cycle progression, and other DNA damage and replication stress responses. ATR signaling is stimulated by an ATR activating protein, and in metazoan cells, there are at least two ATR activators: TOPBP1 and ETAA1. Current evidence indicates TOPBP1 and ETAA1 activate ATR via the same biochemical mechanism, but several aspects of this mechanism remain undefined. For example, ATR and its obligate binding partner ATR interacting protein (ATRIP) form a tetrameric complex consisting of two ATR and two ATRIP molecules, but whether TOPBP1 or ETAA1 dimerization is similarly required for ATR function is unclear. Here, we show that fusion of the TOPBP1 and ETAA1 ATR activation domains (AADs) to dimeric tags makes them more potent activators of ATR in vitro. Furthermore, induced dimerization of both AADs using chemical dimerization of a modified FKBP tag enhances ATR kinase activation and signaling in cells. ETAA1 forms oligomeric complexes mediated by regions of the protein that are predicted to be intrinsically disordered. Induced dimerization of a "mini-ETAA1" protein that contains the AAD and Replication Protein A (RPA) interaction motifs enhances ATR signaling, rescues cellular hypersensitivity to DNA damaging agents, and suppresses micronuclei formation in ETAA1-deficient cells. Together, our results indicate that TOPBP1 and ETAA1 dimerization is important for optimal ATR signaling and genome stability.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.