ArticleMolecular biology of the cell2009
Estrogen inhibits ATR signaling to cell cycle checkpoints and DNA repair.
Article in Molecular biology of the cell, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 86 citations in OpenAlex.
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- IRF7 signalling in tanycytes controls brain-body-immune response across the ovarian cycle.Nature metabolism · 2026Article
- The synthetic estradiol analog E0703 enhancesmLife · 2026Article
- Impact of intraoperative radiotherapy vs postoperative radiotherapy on survival in early-stage breast cancer patients.European radiology · 2026Article
- Inflammaging: triggers, molecular mechanisms, immunological consequences, sex differences, and cutaneous manifestations.Frontiers in immunology · 2025Review
- Proteomic Analysis Reveals Major Proteins and Pathways That Mediate the Effect of 17-β-Estradiol in Cell Division and Apoptosis in Breast Cancer MCF7 Cells.Journal of proteome research · 2024Article
- Testosterone, β-estradiol, and hepatocellular carcinoma: stimulation or inhibition? A comparative effect analysis on cell cycle, apoptosis, and Wnt signaling of HepG2 cells.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Sex- and age-related differences in renal and cardiac injury and senescence in stroke-prone spontaneously hypertensive rats.Biology of sex differences · 2023Article
- Sex difference and immunosenescence affect transplantation outcomes.Frontiers in transplantation · 2023Review
- Pancreatic β-cell senescence in diabetes: mechanisms, markers and therapies.Frontiers in endocrinology · 2023Review
- Review
- Sexual Differentiation Specifies Cellular Responses to DNA Damage.Endocrinology · 2021Review
- A Tale of Ice and Fire: The Dual Role for 17β-Estradiol in Balancing DNA Damage and Genome Integrity.Cancers · 2021Review
- Non-Genomic Actions of Estrogens on the DNA Repair Pathways Are Associated With Chemotherapy Resistance in Breast Cancer.Frontiers in oncology · 2021Review
- Obese Adipose Tissue as a Driver of Breast Cancer Growth and Development: Update and Emerging Evidence.Frontiers in oncology · 2021Review
- The Nexus of Endocrine Signaling and Cancer: How Steroid Hormones Influence Genomic Stability.Endocrinology · 2021Article
- The membrane-associated form of cyclin D1 enhances cellular invasion.Oncogenesis · 2020Article
- Endocrine disrupting chemicals may deregulate DNA repair through estrogen receptor mediated seizing of CBP/p300 acetylase.Journal of endocrinological investigation · 2020Review
- Adverse outcome pathways for ionizing radiation and breast cancer involve direct and indirect DNA damage, oxidative stress, inflammation, genomic instability, and interaction with hormonal regulation of the breast.Archives of toxicology · 2020Review
- DNA damage repair functions and targeted treatment in breast cancer.Breast cancer (Tokyo, Japan) · 2020Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
DNA damage activates the ataxia telangiectasia-mutated and Rad3-related (ATR) kinase signal cascade. How this system is restrained is not understood. We find that in estrogen receptor (ER)-positive breast cancer cells, UV or ionizing radiation and hydroxyurea rapidly activate ATR-dependent phosphorylation of endogenous p53 and Chk1. 17-beta-estradiol (E(2)) substantially blocks ATR activity via plasma membrane-localized ERalpha. E(2)/ER reduces the enhanced association of ATR andTopBP1 proteins that follows DNA damage and strongly correlates to ATR activity. E(2) inhibits ATR activation through rapid PI3K/AKT signaling: AKT phosphorylates TopBP1 at Serine 1159, thereby preventing the enhanced association of ATR with TopBP1 after DNA damage. E(2) also inhibits Claspin:Chk1 protein association via AKT phosphorylation of Chk1, preventing Chk1 signaling to the G2/M checkpoint. ATR-phosphorylation of p53 induces p21 transcription, prevented by E(2)/ER. E(2) delays the assembly and prolongs the resolution of gammaH2AX and Rad51 nuclear foci and delays DNA repair. E(2)/ER also increases the chromosomal damage seen from cell exposure to IR. Therefore, the restraint of ATR cascade activation may be a novel estrogen action relevant to breast cancer.
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Registered trials
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.