ArticleNucleic acids research2023
ADAR1 links R-loop homeostasis to ATR activation in replication stress response.
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Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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27citing papers in PubMed, 1 pooled it
4.0field-weighted citation impact, top 6% of its field
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- The role of R-loops-mediated epigenetic regulation in genome stability maintenance and disease pathogenesis: a systematic review.Epigenetics · 2026Pooled it
- Viral mimicry escape as a necessary feature of malignant transformation.Nature reviews. Cancer · 2026Review
- The DNA/RNA Helicase SETX Maintains R-Loop Homeostasis to Promote Chemoresistance in Ovarian Cancer.Cancer science · 2026Article
- R-Loop Modification and Quantification by Dot Blot.Bio-protocol · 2026Article
- Multi-omics dissection of R-loop dynamics in tumorigenesis: From transcription-replication conflict to therapeutic targets.Molecular therapy. Oncology · 2026Review
- ADAR1 and ADAR2 associate with the RNA exosome and modulate RNA stability.Nucleic acids research · 2026Article
- RPA hyperphosphorylation hinders the resolution of R-loops and G-quadruplex-associated R-loops during RAS-driven senescence.Nucleic acids research · 2026Article
- Redox-driven ADAR1 activation promotes Okazaki fragment maturation and DNA replication integrity.Nature structural & molecular biology · 2026Article
- The role of low-complexity repeats in RNA-RNA interactions and a deep learning framework for duplex prediction.Nature communications · 2026Article
- APOBEC3C coordinates DDX5 in R-loop resolution and dynamic control of Chk1-mediated stress-responsive circuitry as a prerequisite for gemcitabine resistance in p53-deficient cells.Cell death & disease · 2026Article
- Orchestrating innate immunity through RNA editing and helicase activity: ADAR1, dsRNA sensors, and tumor immune evasion.Frontiers in cell and developmental biology · 2026Review
- Genome instability and crosstalk with the immune response.Genome medicine · 2025Review
- PVC Nanoplastics Exposure Exacerbates Asthma through R-Loop Accumulation and Subsequent STING Activation in Macrophages.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Targeting RNA adenosine editing and modification enzymes for RNA therapeutics.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- DNA/RNA-binding protein KIN17 supports esophageal cancer progression via resolving noncanonical STING activation induced by R-loop.Signal transduction and targeted therapy · 2025Article
- Autocrine interferon poisoning mediates ADAR1-dependent synthetic lethality in BRCA1/2-mutant cancers.Nature communications · 2025Article
- Participants in Transcription-Replication Conflict and Their Role in Formation and Resolution of R-Loops.International journal of molecular sciences · 2025Review
- Adar contributes to genome integrity by regulating R-loop homeostasis in Drosophila.BMC biology · 2025Article
- The nonstructural protein 13 of porcine deltacoronavirus coordinates ATP-driven duplex unwinding and ATP-independent strand annealing for nucleic acid remodeling.BMC veterinary research · 2025Article
- Review
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Authors and funding
20 authors at 2 institutions in 1 country.
Biao ZhangState Key Laboratory of Experimental Hematology, Haihe Laboratory of Cell Ecosystem, Key Laboratory of Breast Cancer Prevention and Therapy (Ministry of Education), Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin 300070, China.
Yi LiState Key Laboratory of Experimental Hematology, Haihe Laboratory of Cell Ecosystem, Key Laboratory of Breast Cancer Prevention and Therapy (Ministry of Education), Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin 300070, China.
Jieyou ZhangState Key Laboratory of Experimental Hematology, Haihe Laboratory of Cell Ecosystem, Key Laboratory of Breast Cancer Prevention and Therapy (Ministry of Education), Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin 300070, China.
Yuejiao WangState Key Laboratory of Experimental Hematology, Haihe Laboratory of Cell Ecosystem, Key Laboratory of Breast Cancer Prevention and Therapy (Ministry of Education), Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin 300070, China.
Can LiangState Key Laboratory of Experimental Hematology, Haihe Laboratory of Cell Ecosystem, Key Laboratory of Breast Cancer Prevention and Therapy (Ministry of Education), Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin 300070, China.
Ting LuState Key Laboratory of Experimental Hematology, Haihe Laboratory of Cell Ecosystem, Key Laboratory of Breast Cancer Prevention and Therapy (Ministry of Education), Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin 300070, China.
Chunyong ZhangState Key Laboratory of Experimental Hematology, Haihe Laboratory of Cell Ecosystem, Key Laboratory of Breast Cancer Prevention and Therapy (Ministry of Education), Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin 300070, China.
Ling LiuState Key Laboratory of Experimental Hematology, Haihe Laboratory of Cell Ecosystem, Key Laboratory of Breast Cancer Prevention and Therapy (Ministry of Education), Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin 300070, China.
Yan QinState Key Laboratory of Experimental Hematology, Haihe Laboratory of Cell Ecosystem, Key Laboratory of Breast Cancer Prevention and Therapy (Ministry of Education), Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin 300070, China.
Jiahuan HeTianjin Institutes of Health Science, National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China.
Xiangnan ZhaoState Key Laboratory of Experimental Hematology, Haihe Laboratory of Cell Ecosystem, Key Laboratory of Breast Cancer Prevention and Therapy (Ministry of Education), Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin 300070, China.
Jia YuTianjin Institutes of Health Science, National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China.ORCID 0000-0003-3499-5133
Jihui HaoState Key Laboratory of Experimental Hematology, Haihe Laboratory of Cell Ecosystem, Key Laboratory of Breast Cancer Prevention and Therapy (Ministry of Education), Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin 300070, China.
Jie YangState Key Laboratory of Experimental Hematology, Haihe Laboratory of Cell Ecosystem, Key Laboratory of Breast Cancer Prevention and Therapy (Ministry of Education), Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin 300070, China.ORCID 0000-0002-5301-7610
Mulin Jun LiState Key Laboratory of Experimental Hematology, Haihe Laboratory of Cell Ecosystem, Key Laboratory of Breast Cancer Prevention and Therapy (Ministry of Education), Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin 300070, China.
Zhi YaoState Key Laboratory of Experimental Hematology, Haihe Laboratory of Cell Ecosystem, Key Laboratory of Breast Cancer Prevention and Therapy (Ministry of Education), Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin 300070, China.
Shuai MaState Key Laboratory of Experimental Hematology, Haihe Laboratory of Cell Ecosystem, Key Laboratory of Breast Cancer Prevention and Therapy (Ministry of Education), Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin 300070, China.
Hui ChengState Key Laboratory of Experimental Hematology, Haihe Laboratory of Cell Ecosystem, Key Laboratory of Breast Cancer Prevention and Therapy (Ministry of Education), Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin 300070, China.
Tao ChengState Key Laboratory of Experimental Hematology, Haihe Laboratory of Cell Ecosystem, Key Laboratory of Breast Cancer Prevention and Therapy (Ministry of Education), Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin 300070, China.
Lei ShiState Key Laboratory of Experimental Hematology, Haihe Laboratory of Cell Ecosystem, Key Laboratory of Breast Cancer Prevention and Therapy (Ministry of Education), Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin 300070, China.ORCID 0000-0003-1679-3618
Tianjin Medical University Cancer Institute and Hospital · CNChinese Academy of Medical Sciences & Peking Union Medical College · CN
Funding
CAMS Fundamental Research Funds for Central Research Institutes 3332021093CAMS Initiative for Innovative Medicine 2021-I2M-1-019Haihe Laboratory of Cell Ecosystem Innovation Fund 22HHXBSS00021Ministry of Science and Technology of China 2021YFA1100900National Natural Science Foundation of China 82230101
Abstract
Unscheduled R-loops are a major source of replication stress and DNA damage. R-loop-induced replication defects are sensed and suppressed by ATR kinase, whereas it is not known whether R-loop itself is actively involved in ATR activation and, if so, how this is achieved. Here, we report that the nuclear form of RNA-editing enzyme ADAR1 promotes ATR activation and resolves genome-wide R-loops, a process that requires its double-stranded RNA-binding domains. Mechanistically, ADAR1 interacts with TOPBP1 and facilitates its loading on perturbed replication forks by enhancing the association of TOPBP1 with RAD9 of the 9-1-1 complex. When replication is inhibited, DNA-RNA hybrid competes with TOPBP1 for ADAR1 binding to promote the translocation of ADAR1 from damaged fork to accumulate at R-loop region. There, ADAR1 recruits RNA helicases DHX9 and DDX21 to unwind R-loops, simultaneously allowing TOPBP1 to stimulate ATR more efficiently. Collectively, we propose that the tempo-spatially regulated assembly of ADAR1-nucleated protein complexes link R-loop clearance and ATR activation, while R-loops crosstalk with blocked replication forks by transposing ADAR1 to finetune ATR activity and safeguard the genome.
Indexed as
DNA-Binding ProteinsR-Loop StructuresAdenosine DeaminaseAnimalsAtaxia Telangiectasia Mutated ProteinsCell Cycle ProteinsDNA ReplicationHumansMiceRNARNA-Binding ProteinsADAR protein, humanAdenosine DeaminaseAtaxia Telangiectasia Mutated ProteinsATR protein, humanCell Cycle ProteinsDNA-Binding ProteinsRNARNA-Binding Proteins
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