ArticleMolecular and cellular biology2001
The modified human DNA repair enzyme O(6)-methylguanine-DNA methyltransferase is a negative regulator of estrogen receptor-mediated transcription upon alkylation DNA damage.
Article in Molecular and cellular biology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 2 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 2 syntheses or guidelines pooled it, 69 citations in OpenAlex.
- Pooled it
- MGMT Leu84Phe polymorphism contributes to cancer susceptibility: evidence from 44 case-control studies.PloS one · 2013Pooled it
- Sex and base excision repair as key susceptibility factors for alkylation-induced mutations, toxicity and hepatic cancer.DNA repair · 2026Article
- Sex and Alkyladenine DNA Glycosylase Expression are Key Susceptibility Factors for NDMA-induced Mutations, Toxicity, and Cancer.bioRxiv : the preprint server for biology · 2025Article
- The Versatile Attributes of MGMT: Its Repair Mechanism, Crosstalk with Other DNA Repair Pathways, and Its Role in Cancer.Cancers · 2024Review
- The DNA Alkyltransferase Family of DNA Repair Proteins: Common Mechanisms, Diverse Functions.International journal of molecular sciences · 2023Review
- Leveraging Genetics to Improve Cardiovascular Health in Diabetes: The 2018 Edwin Bierman Award Lecture.Diabetes · 2019Article
- S-phase Specific Downregulation of Human ONeoplasia (New York, N.Y.) · 2018Article
- Heavy metals effect on breast cancer progression.Journal of occupational medicine and toxicology (London, England) · 2017Article
- Genetic Predictors of Cardiovascular Mortality During Intensive Glycemic Control in Type 2 Diabetes: Findings From the ACCORD Clinical Trial.Diabetes care · 2016Article
- Sensitivity to PRIMA-1MET is associated with decreased MGMT in human glioblastoma cells and glioblastoma stem cells irrespective of p53 status.Oncotarget · 2016Article
- New insights into estrogenic regulation ofJournal of biomedical research · 2016Article
- MGMT promoter hypermethylation and K-RAS, PTEN and TP53 mutations in tamoxifen-exposed and non-exposed endometrial cancer cases.British journal of cancer · 2014Article
- Estrogen signaling and the DNA damage response in hormone dependent breast cancers.Frontiers in oncology · 2014Review
- Structural/functional analysis of the human OXR1 protein: identification of exon 8 as the anti-oxidant encoding function.BMC molecular biology · 2012Article
- Multifaceted roles of alkyltransferase and related proteins in DNA repair, DNA damage, resistance to chemotherapy, and research tools.Chemical research in toxicology · 2011Review
- Targeting O⁶-methylguanine-DNA methyltransferase with specific inhibitors as a strategy in cancer therapy.Cellular and molecular life sciences : CMLS · 2010Review
- Apurinic/apyrimidinic endonuclease 1 alters estrogen receptor activity and estrogen-responsive gene expression.Molecular endocrinology (Baltimore, Md.) · 2009Article
- The L84F polymorphic variant of human O6-methylguanine-DNA methyltransferase alters stability in U87MG glioma cells but not temozolomide sensitivity.Neuro-oncology · 2009Article
- Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cell proliferation requires precise control to prevent mutations from replication of (unrepaired) damaged DNA in cells exposed spontaneously to mutagens. Here we show that the modified human DNA repair enzyme O(6)-methylguanine-DNA methyltransferase (R-MGMT), formed from the suicidal repair of the mutagenic O(6)-alkylguanine (6RG) lesions by MGMT in the cells exposed to alkylating carcinogens, functions in such control by preventing the estrogen receptor (ER) from transcription activation that mediates cell proliferation. This function is in contrast to the phosphotriester repair domain of bacterial ADA protein, which acts merely as a transcription activator for its own synthesis upon repair of phosphotriester lesions. First, MGMT, which is constitutively present at active transcription sites, coprecipitates with the transcription integrator CREB-binding protein CBP/p300 but not R-MGMT. Second, R-MGMT, which adopts an altered conformation, utilizes its exposed VLWKLLKVV peptide domain (codons 98 to 106) to bind ER. This binding blocks ER from association with the LXXLL motif of its coactivator, steroid receptor coactivator-1, and thus represses ER effectively from carrying out transcription that regulates cell growth. Thus, through a change in conformation upon repair of the 6RG lesion, MGMT switches from a DNA repair factor to a transcription regulator (R-MGMT), enabling the cell to sense as well as respond to mutagens. These results have implications in chemotherapy and provide insights into the mechanisms for linking transcription suppression with transcription-coupled DNA repair.
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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.