ArticleNature communications2024
Trans-lesion synthesis and mismatch repair pathway crosstalk defines chemoresistance and hypermutation mechanisms in glioblastoma.
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Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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26citing papers in PubMed
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Who cites it
26 citing papers in PubMed.
- Two Faces of UV Mutagenesis: Independent and Collateral Mutagenesis in Skin Cancers.Life (Basel, Switzerland) · 2026Article
- Divergent Roles of Canonical and Non-Canonical Mismatch Repair in Regulating Temozolomide Sensitivity in Glioblastoma.International journal of molecular sciences · 2026Review
- Low YTHDC1 Expression Upregulates FSCN1 to Promote Nuclear F-Actin Formation and Facilitate Double-strand DNA Breaks Repair in TMZ-Resistant Glioblastoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Differential roles of Rad18 in repressing carcinogen- and oncogene-driven mutagenesisNAR cancer · 2026Article
- Article
- Targeting MAD2L2-dependent translesion synthesis impairs DNA damage tolerance and enhances cellular response to cisplatin.Frontiers in cell and developmental biology · 2026Article
- A Comprehensive Analysis of Natural Bioactive Molecules for the Treatment and Control of Glioblastoma Multiforme (GBM) Targeting Underlying Molecular Mechanism.Chemistry & biodiversity · 2026Review
- Defining treatment-resistant brain cancer: Genetic screening to identify oncogene-driven immunomodulation and therapy resistance.Cancer gene therapy · 2026Review
- Cellular heterogeneity and therapeutic response profiling of human IDH + glioma stem cell cultures.Scientific reports · 2025Article
- Differential roles of Rad18 in repressing carcinogen- and oncogene-driven mutagenesisbioRxiv : the preprint server for biology · 2025Article
- Rapid Functional Drug Screening of Passage-Zero Patient Brain Tumor Tissues Ex Vivo: Results from a Clinical Feasibility Study.Research square · 2025Article
- Review
- TRIP12's role in the governance of DNA polymerase β involvement in DNA damage response and repair.Nucleic acids research · 2025Article
- Overcoming temozolomide resistance in glioma: recent advances and mechanistic insights.Acta neuropathologica communications · 2025Review
- Construction and validation of a prognostic model for glioma: an analysis based on mismatch repair-related genes and their correlation with clinicopathological features.Translational cancer research · 2025Article
- TRIP13 protects pancreatic cancer cells against intrinsic and therapy-induced DNA replication stress.NAR cancer · 2025Article
- Opportunities and challenges for patient-derived models of brain tumors in functional precision medicine.NPJ precision oncology · 2025Review
- MAPK14/p38α shapes the molecular landscape of endometrial cancer and promotes tumorigenic characteristics.Cell reports · 2025Article
- Nonrepair functions of DNA mismatch repair proteins: new avenues for precision oncology.Trends in cancer · 2025Review
- The interplay of mitochondrial dysfunction and altered metabolic pathways in glioblastoma.Contemporary oncology (Poznan, Poland) · 2025Review
Corrections and comments
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Authors and funding
23 authors.
Xing Cheng *Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC, 27599, USA.ORCID 0000-0002-2389-2377
Jing An *Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC, 27599, USA.ORCID 0000-0002-1265-2474
Jitong Lou *Department of Biostatistics, University of North Carolina, Chapel Hill, NC, 27599, USA.ORCID 0000-0002-1049-0416
Qisheng Gu *Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Shanghai, China.ORCID 0000-0001-7294-042X
Weimin DingLineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, 27599, USA.
Gaith Nabil DrobyDepartment of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC, 27599, USA.ORCID 0000-0003-0116-0340
Yilin WangDepartment of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC, 27599, USA.ORCID 0000-0002-1255-767X
Chenghao WangDepartment of Biostatistics, University of North Carolina, Chapel Hill, NC, 27599, USA.
Yanzhe GaoDepartment of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC, 27599, USA.
Jay Ramanlal AnandDepartment of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC, 27599, USA.ORCID 0000-0003-2071-9891
Abigail SheltonDepartment of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC, 27599, USA.
Andrew Benson SatterleeEshelman School of Pharmacy, Division of Pharmacoengineering and Molecular Pharmaceutics, University of North Carolina, Chapel Hill, NC, 27599, USA.
Breanna MannEshelman School of Pharmacy, Division of Pharmacoengineering and Molecular Pharmaceutics, University of North Carolina, Chapel Hill, NC, 27599, USA.ORCID 0000-0002-6486-3230
Yun-Chung HsiaoDepartment of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.ORCID 0000-0003-1189-6511
Chih-Wei LiuDepartment of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.ORCID 0000-0002-0823-0252
Kun LuDepartment of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Shawn HingtgenEshelman School of Pharmacy, Division of Pharmacoengineering and Molecular Pharmaceutics, University of North Carolina, Chapel Hill, NC, 27599, USA.ORCID 0000-0003-4355-2377
Jiguang WangDivision of Life Science, Department of Chemical and Biological Engineering, State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong SAR, China.ORCID 0000-0002-6923-4097
Zhaoliang LiuInstitute of Cancer Prevention and Treatment, Heilongjiang Academy of Medical Sciences, Harbin Medical University, Harbin, China.ORCID 0000-0002-2074-1522
C Ryan MillerDepartment of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC, 27599, USA.ORCID 0000-0002-0096-8762
Di WuDepartment of Biostatistics, University of North Carolina, Chapel Hill, NC, 27599, USA.ORCID 0000-0001-8331-2357
Cyrus VaziriDepartment of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC, 27599, USA. cyrus_vaziri@med.unc.edu.ORCID 0000-0002-3081-8685
Yang YangDepartment of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC, 27599, USA. yangyang@email.unc.edu.ORCID 0000-0002-5936-4090
Funding
Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI David Darr · 1985 to 2026
$201.5MNorth Carolina Translational & Clinical Sciences Institute (NC TraCS)UL1TR001111 · NCATS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BUSE, JOHN BERNARD, CAREY, TIMOTHY S · 2013 to 2017
$43.9MUNC-CH CENTER FOR ENVIRONMENTAL HEALTH &SUSCEPTIBILITYP30ES010126 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Stephanie Engel · 2001 to 2026
$36.3MThe UNC Chapel Hill Superfund Research Program (UNC-SRP)P42ES031007 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Rebecca Fry · 2020 to 2026
$22.2MA Novel Carcinogen-Induced Cell Cycle CheckpointR01ES009558 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI VAZIRI, CYRUS · 2002 to 2016
$4.8MA consortium effort to translate therapies for neurological diseases via an ex vivo organotypic platformU01TR003715 · NCATS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BALDWIN, ALBERT SIDNEY, FLORES, CATHERINE T · 2021 to 2024
$4.6MDefining Mechanisms of Pathological Trans-Lesion Synthesis During CarcinogenesisR01CA215347 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI VAZIRI, CYRUS, WILLIAMS, SCOTT E · 2018 to 2022
$2.6MEstablishing MAGE-A4/RAD18 as a novel cancer-specific chemotherapeutic targetR01CA229530 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI PEARCE, KENNETH HUGH, VAZIRI, CYRUS · 2019 to 2023
$2.0MAndor Dragonfly 202 Spinning Disk Confocal Microscope for the University of North Carolina at Chapel HillS10OD030223 · OD · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ARIEL, PABLO · 2021 to 2021
$474kNOVEL CARCINOGEN INDUCED CELL CYCLE CHECKPOINTR29ES009558 · NIEHS · BOSTON UNIVERSITY MEDICAL CAMPUS · PI VAZIRI, CYRUS · 1998 to 2001
$221kNCATS NIH HHS U01 TR003715NCATS NIH HHS UL1 TR001111NCI NIH HHS P30 CA016086NCI NIH HHS R01 CA215347NCI NIH HHS R01 CA229530NIEHS NIH HHS P30 ES010126NIEHS NIH HHS P42 ES031007NIEHS NIH HHS R01 ES009558NIEHS NIH HHS R29 ES009558NIH HHS S10 OD030223
Abstract
Almost all Glioblastoma (GBM) are either intrinsically resistant to the chemotherapeutical drug temozolomide (TMZ) or acquire therapy-induced mutations that cause chemoresistance and recurrence. The genome maintenance mechanisms responsible for GBM chemoresistance and hypermutation are unknown. We show that the E3 ubiquitin ligase RAD18 (a proximal regulator of TLS) is activated in a Mismatch repair (MMR)-dependent manner in TMZ-treated GBM cells, promoting post-replicative gap-filling and survival. An unbiased CRISPR screen provides an aerial map of RAD18-interacting DNA damage response (DDR) pathways deployed by GBM to tolerate TMZ genotoxicity. Analysis of mutation signatures from TMZ-treated GBM reveals a role for RAD18 in error-free bypass of O
Indexed as
GlioblastomaDNA-Binding ProteinsDNA Mismatch RepairDrug Resistance, NeoplasmHumansTemozolomideTranslesion DNA SynthesisUbiquitin-Protein LigasesDNA-Binding ProteinsRAD18 protein, humanTemozolomideUbiquitin-Protein Ligases
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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.