ArticleNature2017
A ubiquitin-dependent signalling axis specific for ALKBH-mediated DNA dealkylation repair.
Article in Nature, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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The trial behind it
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Who cites it
61 citing papers in PubMed, 113 citations in OpenAlex.
- E3 ligase LMO7 promotes ALKBH2 ubiquitination to sensitize MGMT-deficient glioblastoma to temozolomide.Cell death & disease · 2026Article
- DUSP12 promotes cell cycle progression and protects cells from ZNF622 mediated apoptosis.Cell death & disease · 2026Article
- ASCC3 promotes chemosensitivity in colorectal cancer cells.Scientific reports · 2026Article
- Ribosome-associated quality control and related mechanisms.Nature structural & molecular biology · 2026Review
- A novel spliceosomopathy caused by de novo SF3B3 variants.Genome medicine · 2026Article
- KDM7B-mediated demethylation of RNF113A regulates small cell lung cancer sensitivity to alkylation damage.bioRxiv : the preprint server for biology · 2026Article
- Histone modification-regulated LncRNA DLEU1 interacts with ASCC2/ALKBH3 complex to drive DNA repair, antioxidant homeostasis and glucose metabolism in gastric cancer.Biomarker research · 2026Article
- Human MutLα activates methylpurine DNA glycosylase to induce alkylation damage cytotoxicity.bioRxiv : the preprint server for biology · 2025Article
- CRISPR activation of the ribosome-associated quality control factor ASCC3 ameliorates fragile X syndrome phenotypes in mice.Science translational medicine · 2025Article
- Proteome-Wide Identification ofAnalytical chemistry · 2025Article
- Whole genome sequencing analysis of body mass index identifies novel African ancestry-specific risk allele.Nature communications · 2025Article
- YTHDC1 cooperates with the THO complex to prevent RNA-damage-induced DNA breaks.Molecular cell · 2025Article
- Integrative multi-omics analysis and machine learning reveal the unique role of ASCC3 in combination with various immune-related genes in rectal adenocarcinoma.Frontiers in genetics · 2025Article
- Alternative polyadenylation regulates the translation of metabolic and inflammation-related proteins in adipose tissue of gestational diabetes mellitus.Computational and structural biotechnology journal · 2024Article
- Epitranscriptome in action: RNA modifications in the DNA damage response.Molecular cell · 2024Review
- Small Cell Lung Cancer-An Update on Chemotherapy Resistance.Current treatment options in oncology · 2024Review
- The face of Non-photosensitive trichothiodystrophy phenotypic spectrum: A subsequent study on paediatric population.Molecular genetics & genomic medicine · 2024Article
- A ubiquitin language communicates ribosomal distress.Seminars in cell & developmental biology · 2024Review
- Effect of RNF113A deficiency on oxidative stress-induced NRF2 pathway.Animal cells and systems · 2024Article
- ASCC3 promotes the immunosuppression and progression of non-small cell lung cancer by impairing the type I interferon response via CAND1-mediated ubiquitination inhibition of STAT3.Journal for immunotherapy of cancer · 2023Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 8 institutions in 3 countries.
Funding
Abstract
DNA repair is essential to prevent the cytotoxic or mutagenic effects of various types of DNA lesions, which are sensed by distinct pathways to recruit repair factors specific to the damage type. Although biochemical mechanisms for repairing several forms of genomic insults are well understood, the upstream signalling pathways that trigger repair are established for only certain types of damage, such as double-stranded breaks and interstrand crosslinks. Understanding the upstream signalling events that mediate recognition and repair of DNA alkylation damage is particularly important, since alkylation chemotherapy is one of the most widely used systemic modalities for cancer treatment and because environmental chemicals may trigger DNA alkylation. Here we demonstrate that human cells have a previously unrecognized signalling mechanism for sensing damage induced by alkylation. We find that the alkylation repair complex ASCC (activating signal cointegrator complex) relocalizes to distinct nuclear foci specifically upon exposure of cells to alkylating agents. These foci associate with alkylated nucleotides, and coincide spatially with elongating RNA polymerase II and splicing components. Proper recruitment of the repair complex requires recognition of K63-linked polyubiquitin by the CUE (coupling of ubiquitin conjugation to ER degradation) domain of the subunit ASCC2. Loss of this subunit impedes alkylation adduct repair kinetics and increases sensitivity to alkylating agents, but not other forms of DNA damage. We identify RING finger protein 113A (RNF113A) as the E3 ligase responsible for upstream ubiquitin signalling in the ASCC pathway. Cells from patients with X-linked trichothiodystrophy, which harbour a mutation in RNF113A, are defective in ASCC foci formation and are hypersensitive to alkylating agents. Together, our work reveals a previously unrecognized ubiquitin-dependent pathway induced specifically to repair alkylation damage, shedding light on the molecular mechanism of X-linked trichothiodystrophy.
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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.