ArticleGenome research2017
Genome-wide TOP2A DNA cleavage is biased toward translocated and highly transcribed loci.
Article in Genome research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 59 citations in OpenAlex.
- Complex mechanisms of topoisomerase II poisons revealed by whole-genome analysis.Communications biology · 2026Article
- Top2a-dependent neuronal regulation of social behavior and persistent rescue of social deficit through PRC2-mediated epigenetic reprogramming.bioRxiv : the preprint server for biology · 2026Article
- TOP2B modulates DNA supercoiling and chromatin contacts during transcriptional induction.Science advances · 2025Article
- α-Hemolysin from Staphylococcus aureus Changes the Epigenetic Landscape of Th17 Cells.ImmunoHorizons · 2024Article
- Expression and potential molecular mechanism of TOP2A in metastasis of non-small cell lung cancer.Scientific reports · 2024Article
- The Bisdioxopiperazine ICRF-193 Attenuates LPS-induced IL-1β Secretion by Macrophages.Inflammation · 2024Article
- Topological regulation of the estrogen transcriptional response by ZATT-mediated inhibition of TOP2B activity.bioRxiv : the preprint server for biology · 2024Article
- Telling Your Right Hand from Your Left: The Effects of DNA Supercoil Handedness on the Actions of Type II Topoisomerases.International journal of molecular sciences · 2023Review
- Basis for the discrimination of supercoil handedness during DNA cleavage by human and bacterial type II topoisomerases.Nucleic acids research · 2023Article
- Article
- Top2a promotes the development of social behavior via PRC2 and H3K27me3.Science advances · 2022Article
- Untangling the roles of TOP2A and TOP2B in transcription and cancer.Science advances · 2022Review
- Recognition of DNA Supercoil Handedness during Catenation Catalyzed by Type II Topoisomerases.Biochemistry · 2022Article
- Recurrent mutations in topoisomerase IIα cause a previously undescribed mutator phenotype in human cancers.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- KMT2A-MAML2 rearrangement emerged and regressed during neuroblastoma therapy without leukemia after 12.8-year follow-up.Pediatric blood & cancer · 2022Article
- Predicting candidate therapeutic drugs for sepsis-induced acute respiratory distress syndrome based on transcriptome profiling.Bioengineered · 2021Article
- Identification of potential biomarkers associated with immune infiltration in papillary renal cell carcinoma.Journal of clinical laboratory analysis · 2021Article
- TOP2B Enzymatic Activity on Promoters and Introns Modulates Multiple Oncogenes in Human Gliomas.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Article
- A Role for VCP/p97 in the Processing of Drug-Stabilized TOP2-DNA Covalent Complexes.Molecular pharmacology · 2021Article
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Type II topoisomerases orchestrate proper DNA topology, and they are the targets of anti-cancer drugs that cause treatment-related leukemias with balanced translocations. Here, we develop a high-throughput sequencing technology to define TOP2 cleavage sites at single-base precision, and use the technology to characterize TOP2A cleavage genome-wide in the human K562 leukemia cell line. We find that TOP2A cleavage has functionally conserved local sequence preferences, occurs in cleavage cluster regions (CCRs), and is enriched in introns and lincRNA loci. TOP2A CCRs are biased toward the distal regions of gene bodies, and TOP2 poisons cause a proximal shift in their distribution. We find high TOP2A cleavage levels in genes involved in translocations in TOP2 poison-related leukemia. In addition, we find that a large proportion of genes involved in oncogenic translocations overall contain TOP2A CCRs. The TOP2A cleavage of coding and lincRNA genes is independently associated with both length and transcript abundance. Comparisons to ENCODE data reveal distinct TOP2A CCR clusters that overlap with marks of transcription, open chromatin, and enhancers. Our findings implicate TOP2A cleavage as a broad DNA damage mechanism in oncogenic translocations as well as a functional role of TOP2A cleavage in regulating transcription elongation and gene activation.
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