ArticleNature cell biology2024
C-to-G editing generates double-strand breaks causing deletion, transversion and translocation.
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Article in Nature cell biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 29 papers.
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29citing papers in PubMed
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29 citing papers in PubMed, 40 citations in OpenAlex.
- A self-iterative orthogonal base-editing platform enables multiplex N-to-N diversification and genome-scale functional screening in Escherichia coli.Nucleic acids research · 2026Article
- Precise dual-gene knockout of MSTN and SOCS2 via cytidine base editing enhances muscling and growth in goats.Functional & integrative genomics · 2026Article
- Targeted DNA ADP-ribosylation triggers templated repair in bacteria and base mutagenesis in eukaryotes.Nature biotechnology · 2026Article
- Distinct repair outcomes from single and convergent replication fork collapse.Nature structural & molecular biology · 2026Article
- Simultaneous orthogonal cell engineering by a single CRISPR-Cas9 polyfunctional editor.Nature communications · 2026Article
- Deep Prior Framework: integrating functional specificity with general plausibility for targeted protein evolution.Briefings in bioinformatics · 2026Article
- Epigenetic editing: from concept to clinic.Nature reviews. Drug discovery · 2026Review
- Single-cell multiplex approaches deeply map ON-target CRISPR-genotoxicity and reveal its mitigation by palbociclib and long-term engraftment.Nature communications · 2026Article
- Harnessing the potential of gene editing technology for CAR-T cell therapy of solid tumors.Inflammation and regeneration · 2025Review
- Genome editing with the HDR-enhancing DNA-PKcs inhibitor AZD7648 causes large-scale genomic alterations.Nature biotechnology · 2025Article
- The editable landscape of the yeast genome reveals hotspots of structural variant formation.Science advances · 2025Article
- Multiplex base editing of BCL11A regulatory elements to treat sickle cell disease.Cell reports. Medicine · 2025Article
- Programmable epigenome editing by transient delivery of CRISPR epigenome editor ribonucleoproteins.Nature communications · 2025Article
- ONE-STEP tagging: a versatile method for rapid site-specific integration by simultaneous reagent delivery.Nucleic acids research · 2025Article
- Elucidating the genetic mechanisms governing cytosine base editing outcomes through CRISPRi screens.Nature communications · 2025Article
- Targeted deaminase-free T-to-G and C-to-K base editing in rice by fused human uracil DNA glycosylase variants.Plant biotechnology journal · 2025Article
- Patterns of spontaneous and induced genomic alterations inApplied and environmental microbiology · 2025Article
- Rewriting the script: gene therapy and genome editing for von Willebrand Disease.Frontiers in genome editing · 2025Review
- Adenine base editors induce off-target structure variations in mouse embryos and primary human T cells.Genome biology · 2024Article
- Molecular mechanisms of DNA lesion and repair during antibody somatic hypermutation.Science China. Life sciences · 2024Review
Corrections and comments
- Erratum issued
Authors and funding
30 authors at 6 institutions in 2 countries.
Min Emma Huang *Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, China.ORCID http://orcid.org/0009-0008-5722-6197
Yining Qin *Key Laboratory of RNA Science and Engineering, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of SciencesUniversity of Chinese Academy of Sciences, Shanghai, China.
Yafang Shang *Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, China.
Qian HaoDepartment of Immunology and Microbiology, Shanghai Institute of Immunology, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Chuanzong ZhanDepartment of Immunology and Microbiology, Shanghai Institute of Immunology, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Chaoyang LianDepartment of Immunology and Microbiology, Shanghai Institute of Immunology, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Simin LuoDepartment of Immunology and Microbiology, Shanghai Institute of Immunology, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Liu Daisy LiuKey Laboratory of RNA Science and Engineering, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of SciencesUniversity of Chinese Academy of Sciences, Shanghai, China.
Senxin ZhangDepartment of Mathematics, Shanghai Normal University, Shanghai, China.
Yu ZhangDepartment of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yang WoDepartments of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, Institute of Thoracic Oncology, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Niu LiDepartment of Medical Genetics and Molecular Diagnostic Laboratory, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shuheng WuKey Laboratory of RNA Science and Engineering, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of SciencesUniversity of Chinese Academy of Sciences, Shanghai, China.
Tuantuan GuiDepartment of Immunology and Microbiology, Shanghai Institute of Immunology, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Binbin WangDepartment of Immunology and Microbiology, Shanghai Institute of Immunology, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yifeng LuoKey Laboratory of RNA Science and Engineering, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of SciencesUniversity of Chinese Academy of Sciences, Shanghai, China.
Yanni CaiKey Laboratory of RNA Science and Engineering, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of SciencesUniversity of Chinese Academy of Sciences, Shanghai, China.
Xiaojing LiuKey Laboratory of RNA Science and Engineering, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of SciencesUniversity of Chinese Academy of Sciences, Shanghai, China.
Ziye XuKey Laboratory of RNA Science and Engineering, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of SciencesUniversity of Chinese Academy of Sciences, Shanghai, China.
Pengfei DaiKey Laboratory of RNA Science and Engineering, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of SciencesUniversity of Chinese Academy of Sciences, Shanghai, China.
Simiao LiKey Laboratory of RNA Science and Engineering, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of SciencesUniversity of Chinese Academy of Sciences, Shanghai, China.
Liang ZhangHefei National Research Center for Cross Disciplinary Science, Ministry of Education Key Laboratory for Membraneless Organelles and Cellular Dynamics, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.ORCID http://orcid.org/0000-0002-8338-784X
Junchao DongDepartment of Immunology and Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
Jian WangInternational Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Xiaoqi ZhengCenter for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yingjie XuDepartment of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yihua SunDepartments of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, Institute of Thoracic Oncology, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.ORCID http://orcid.org/0000-0002-5287-0601
Wei WuKey Laboratory of RNA Science and Engineering, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of SciencesUniversity of Chinese Academy of Sciences, Shanghai, China.
Leng-Siew YeapDepartment of Immunology and Microbiology, Shanghai Institute of Immunology, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Shanghai, China. yeaplengsiew@shsmu.edu.cn.ORCID http://orcid.org/0000-0003-4914-7428
Fei-Long MengKey Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, China. feilong.meng@sibcb.ac.cn.ORCID http://orcid.org/0000-0003-0333-6872
Center for Excellence in Molecular Cell Science · CNShanghai Jiao Tong University · CNFudan University Shanghai Cancer Center · CNShanghai Normal University · CNSun Yat-sen University · CNUniversity of Science and Technology of China · CN
Funding
Chinese Academy of Sciences (CAS) JCTD-2020-17National Natural Science Foundation of China (National Science Foundation of China) 31722020National Natural Science Foundation of China (National Science Foundation of China) 31970880National Natural Science Foundation of China (National Science Foundation of China) 32090040National Natural Science Foundation of China (National Science Foundation of China) 32170884National Natural Science Foundation of China (National Science Foundation of China) 32325019National Natural Science Foundation of China (National Science Foundation of China) 81861138014Natural Science Foundation of Shanghai (Natural Science Foundation of Shanghai Municipality) 23XD1424000Science and Technology Commission of Shanghai Municipality (Shanghai Municipal Science and Technology Commission) HS2021SHZX001
Abstract
Base editors (BEs) introduce base substitutions without double-strand DNA cleavage. Besides precise substitutions, BEs generate low-frequency 'stochastic' byproducts through unclear mechanisms. Here, we performed in-depth outcome profiling and genetic dissection, revealing that C-to-G BEs (CGBEs) generate substantial amounts of intermediate double-strand breaks (DSBs), which are at the centre of several byproducts. Imperfect DSB end-joining leads to small deletions via end-resection, templated insertions or aberrant transversions during end fill-in. Chromosomal translocations were detected between the editing target and off-targets of Cas9/deaminase origin. Genetic screenings of DNA repair factors disclosed a central role of abasic site processing in DSB formation. Shielding of abasic sites by the suicide enzyme HMCES reduced CGBE-initiated DSBs, providing an effective way to minimize DSB-triggered events without affecting substitutions. This work demonstrates that CGBEs can initiate deleterious intermediate DSBs and therefore require careful consideration for therapeutic applications, and that HMCES-aided CGBEs hold promise as safer tools.
Indexed as
Alkanesulfonic AcidsDNA Breaks, Double-StrandedTranslocation, GeneticCRISPR-Cas SystemsDNA End-Joining RepairDNA RepairHumansAlkanesulfonic AcidsBES
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