ArticleIntegrative biology : quantitative biosciences from nano to macro2012
O6-Methylguanine DNA lesions induce an intra-S-phase arrest from which cells exit into apoptosis governed by early and late multi-pathway signaling network activation.
Article in Integrative biology : quantitative biosciences from nano to macro, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Glioblastoma multiforme (GBM): An overview of current therapies and mechanisms of resistance.Pharmacological research · 2021Pooled it
- Evaluation of Mutation Risk Using Patient-Derived Organoids in Patients With Lynch Syndrome.International journal of cancer · 2026Article
- Persistent interferon signaling and clonal expansion mark early events in DNA methylation damage-induced liver cancer.NAR cancer · 2026Article
- Mismatch repair deficiency drives malignant progression and alters the tumor immune microenvironment in glioblastoma models.The Journal of clinical investigation · 2026Article
- Clinical outcomes of adding vincristine to procarbazine-lomustine in patients with gliomas: insights from current evidence.Ecancermedicalscience · 2026Article
- Feedforward miR-181d degradation modulates population variance of methyl-guanine methyl transferase and temozolomide resistance.Cell reports · 2025Article
- Persistent interferon signaling and clonal expansion mark early events in DNA methylation damage-induced liver cancer.bioRxiv : the preprint server for biology · 2025Article
- Trans-lesion synthesis and mismatch repair pathway crosstalk defines chemoresistance and hypermutation mechanisms in glioblastoma.Nature communications · 2024Article
- Temozolomide, Procarbazine and Nitrosoureas in the Therapy of Malignant Gliomas: Update of Mechanisms, Drug Resistance and Therapeutic Implications.Journal of clinical medicine · 2023Review
- Trans-Lesion Synthesis and Mismatch Repair Pathway Crosstalk Defines Chemoresistance and Hypermutation Mechanisms in Glioblastoma.bioRxiv : the preprint server for biology · 2023Article
- Article
- Article
- Article
- Biological Basis for Threshold Responses to Methylating Agents.Chemical research in toxicology · 2020Review
- In search of effective therapies to overcome resistance to Temozolomide in brain tumours.Cancer drug resistance (Alhambra, Calif.) · 2019Review
- Fluorescent reporter assays provide direct, accurate, quantitative measurements of MGMT status in human cells.PloS one · 2019Article
- HDAC8 affects MGMT levels in glioblastoma cell linesGenes & cancer · 2019Article
- Persistence of DNA adducts, hypermutation and acquisition of cellular resistance to alkylating agents in glioblastoma.Cancer biology & therapy · 2017Review
- ATPase activity of Plasmodium falciparum MLH is inhibited by DNA-interacting ligands and dsRNAs of MLH along with UvrD curtail malaria parasite growth.Protoplasma · 2017Article
- Modulation of urokinase plasminogen activator system by poly(ADP-ribose)polymerase-1 inhibition.Cytotechnology · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The O(6)-methylguanine (O(6)MeG) DNA lesion is well known for its mutagenic, carcinogenic, and cytotoxic properties, and understanding how a cell processes such damage is of critical importance for improving current cancer therapy. Here we use human cells differing only in their O(6)MeG DNA methyltransferase (MGMT) or mismatch repair (MMR) status to explore the O(6)MeG/MMR-dependent molecular and cellular responses to treatment with the methylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). We find that O(6)MeG triggers MMR-dependent cell cycle perturbations in both the first and second cell cycle post treatment. At lower levels of damage, we show that a transient arrest in the second S-phase precedes survival and progression into subsequent cell cycles. However, at higher levels of damage, arrest in the second S-phase coincides with a cessation of DNA replication followed by initiation of apoptotic cell death. Further, we show that entry into apoptotic cell death is specifically from S-phase of the second cell cycle. Finally, we demonstrate the key role of an O(6)MeG/MMR-dependent multi-pathway, multi-time-scale signaling network activation, led by early ATM, H2AX, CHK1, and p53 phosphorylation and followed by greatly amplified late phosphorylation of the early pathway nodes along with activation of the CHK2 kinase and the stress-activated JNK kinase.
Indexed as
Identifiers
What OpenQuestion holds
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.