{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T01:50:22Z","timestamp":1791597022456,"version":"4.3.4"},"reference-count":106,"publisher":"Elsevier BV","issue":"9","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["Z01 BC 006161-17"],"award-info":[{"award-number":["Z01 BC 006161-17"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["Z01 BC 006150-19"],"award-info":[{"award-number":["Z01 BC 006150-19"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["iScience"],"published-print":{"date-parts":[[2026,9]]},"DOI":"10.1016\/j.isci.2026.117168","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T17:57:13Z","timestamp":1786730233000},"page":"117168","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genome-wide mapping reveals increased R-loops in topoisomerase III-beta-deficient human cells"],"prefix":"10.1016","volume":"29","author":[{"given":"Sourav","family":"Saha","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anjali","family":"Dhall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shar-yin Naomi","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liton Kumar","family":"Saha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md Rasel","family":"Al Mahmud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongliang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yilun","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3108-0758","authenticated-orcid":false,"given":"Yves","family":"Pommier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.isci.2026.117168_bib1","doi-asserted-by":"crossref","first-page":"4684","DOI":"10.1074\/jbc.REV119.006364","article-title":"Emerging roles for R-loop structures in the management of topological stress","volume":"295","author":"Chedin","year":"2020","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.isci.2026.117168_bib2","doi-asserted-by":"crossref","first-page":"2271","DOI":"10.1016\/j.jmb.2020.02.014","article-title":"Ultra-deep Coverage Single-molecule R-loop Footprinting Reveals Principles of R-loop Formation","volume":"432","author":"Malig","year":"2020","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.isci.2026.117168_bib3","doi-asserted-by":"crossref","DOI":"10.1093\/narcan\/zcad013","article-title":"R-loops, type I topoisomerases and cancer","volume":"5","author":"Saha","year":"2023","journal-title":"NAR Cancer"},{"key":"10.1016\/j.isci.2026.117168_bib4","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.molcel.2016.05.032","article-title":"Prevalent, Dynamic, and Conserved R-Loop Structures Associate with Specific Epigenomic Signatures in Mammals","volume":"63","author":"Sanz","year":"2016","journal-title":"Mol. Cell"},{"key":"10.1016\/j.isci.2026.117168_bib5","doi-asserted-by":"crossref","DOI":"10.1016\/j.dnarep.2021.103182","article-title":"Defining R-loop classes and their contributions to genome instability","volume":"106","author":"Castillo-Guzman","year":"2021","journal-title":"DNA Repair"},{"key":"10.1016\/j.isci.2026.117168_bib6","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkaa500","article-title":"qDRIP: a method to quantitatively assess RNA-DNA hybrid formation genome-wide","volume":"48","author":"Crossley","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.isci.2026.117168_bib7","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1004288","article-title":"Genome-wide profiling of yeast DNA:RNA hybrid prone sites with DRIP-chip","volume":"10","author":"Chan","year":"2014","journal-title":"PLoS Genet."},{"key":"10.1016\/j.isci.2026.117168_bib8","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1016\/j.molcel.2012.01.017","article-title":"R-loop formation is a distinctive characteristic of unmethylated human CpG island promoters","volume":"45","author":"Ginno","year":"2012","journal-title":"Mol. Cell"},{"key":"10.1016\/j.isci.2026.117168_bib9","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1186\/s13059-018-1478-1","article-title":"DNA Topoisomerase I differentially modulates R-loops across the human genome","volume":"19","author":"Manzo","year":"2018","journal-title":"Genome Biol."},{"key":"10.1016\/j.isci.2026.117168_bib10","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1101\/gad.280834.116","article-title":"S1-DRIP-seq identifies high expression and polyA tracts as major contributors to R-loop formation","volume":"30","author":"Wahba","year":"2016","journal-title":"Genes Dev."},{"key":"10.1016\/j.isci.2026.117168_bib11","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1038\/ni919","article-title":"R-loops at immunoglobulin class switch regions in the chromosomes of stimulated B cells","volume":"4","author":"Yu","year":"2003","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.isci.2026.117168_bib12","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1016\/j.jmb.2010.02.029","article-title":"Mammalian mitochondrial DNA replication intermediates are essentially duplex but contain extensive tracts of RNA\/DNA hybrid","volume":"397","author":"Pohjoism\u00e4ki","year":"2010","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.isci.2026.117168_bib13","doi-asserted-by":"crossref","first-page":"3135","DOI":"10.1002\/j.1460-2075.1996.tb00676.x","article-title":"RNA-DNA hybrid formation at the human mitochondrial heavy-strand origin ceases at replication start sites: an implication for RNA-DNA hybrids serving as primers","volume":"15","author":"Xu","year":"1996","journal-title":"EMBO J."},{"key":"10.1016\/j.isci.2026.117168_bib14","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/j.molcel.2017.12.030","article-title":"Senataxin Mutation Reveals How R-Loops Promote Transcription by Blocking DNA Methylation at Gene Promoters","volume":"69","author":"Grunseich","year":"2018","journal-title":"Mol. Cell"},{"key":"10.1016\/j.isci.2026.117168_bib15","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/s41580-019-0206-3","article-title":"Regulatory R-loops as facilitators of gene expression and genome stability","volume":"21","author":"Niehrs","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.isci.2026.117168_bib16","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1016\/j.molcel.2011.04.026","article-title":"Human Senataxin Resolves RNA\/DNA Hybrids Formed at Transcriptional Pause Sites to Promote Xrn2-Dependent Termination","volume":"42","author":"Skourti-Stathaki","year":"2011","journal-title":"Mol. Cell"},{"key":"10.1016\/j.isci.2026.117168_bib17","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.molcel.2019.01.024","article-title":"R-Loops as Cellular Regulators and Genomic Threats","volume":"73","author":"Crossley","year":"2019","journal-title":"Mol. Cell"},{"key":"10.1016\/j.isci.2026.117168_bib18","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1126\/science.aan6490","article-title":"A mitosis-specific and R loop-driven ATR pathway promotes faithful chromosome segregation","volume":"359","author":"Kabeche","year":"2018","journal-title":"Science"},{"key":"10.1016\/j.isci.2026.117168_bib19","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1038\/s41556-021-00663-4","article-title":"R-loops as Janus-faced modulators of DNA repair","volume":"23","author":"Marnef","year":"2021","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.isci.2026.117168_bib20","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1016\/j.cell.2016.10.001","article-title":"Transient RNA-DNA Hybrids Are Required for Efficient Double-Strand Break Repair","volume":"167","author":"Ohle","year":"2016","journal-title":"Cell"},{"key":"10.1016\/j.isci.2026.117168_bib21","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1080\/15384101.2021.1962638","article-title":"The makings of TERRA R-loops at chromosome ends","volume":"20","author":"Fernandes","year":"2021","journal-title":"Cell Cycle"},{"key":"10.1016\/j.isci.2026.117168_bib22","article-title":"Mitotic R-loops direct Aurora B kinase to maintain centromeric cohesionp","author":"Moran","year":"2021","journal-title":"bioRxiv"},{"key":"10.1016\/j.isci.2026.117168_bib23","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/s41580-022-00452-3","article-title":"Human topoisomerases and their roles in genome stability and organization","volume":"23","author":"Pommier","year":"2022","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.isci.2026.117168_bib24","first-page":"2704","article-title":"Topoisomerase 3beta is the major topoisomerase for mRNAs and linked to neurodevelopment and mental dysfunction","volume":"45","author":"Ahmad","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.isci.2026.117168_bib25","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1080\/15476286.2017.1330741","article-title":"Type IA topoisomerases can be \u201cmagicians\u201d for both DNA and RNA in all domains of life","volume":"14","author":"Ahmad","year":"2017","journal-title":"RNA Biol."},{"key":"10.1016\/j.isci.2026.117168_bib26","doi-asserted-by":"crossref","first-page":"6335","DOI":"10.1093\/nar\/gkw508","article-title":"RNA topoisomerase is prevalent in all domains of life and associates with polyribosomes in animals","volume":"44","author":"Ahmad","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.isci.2026.117168_bib27","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2020.108569","article-title":"DNA and RNA Cleavage Complexes and Repair Pathway for TOP3B RNA- and DNA-Protein Crosslinks","volume":"33","author":"Saha","year":"2020","journal-title":"Cell Rep."},{"key":"10.1016\/j.isci.2026.117168_bib28","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1038\/nn.3484","article-title":"Deletion of TOP3beta, a component of FMRP-containing mRNPs, contributes to neurodevelopmental disorders","volume":"16","author":"Stoll","year":"2013","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.isci.2026.117168_bib29","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1038\/nn.3479","article-title":"Top3beta is an RNA topoisomerase that works with fragile X syndrome protein to promote synapse formation","volume":"16","author":"Xu","year":"2013","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.isci.2026.117168_bib30","doi-asserted-by":"crossref","DOI":"10.1098\/rsob.190222","article-title":"Loss of TOP3B leads to increased R-loop formation and genome instability","volume":"9","author":"Zhang","year":"2019","journal-title":"Open Biol."},{"key":"10.1016\/j.isci.2026.117168_bib31","doi-asserted-by":"crossref","first-page":"3061","DOI":"10.1093\/nar\/gky103","article-title":"Arginine methylation of the C-terminus RGG motif promotes TOP3B topoisomerase activity and stress granule localization","volume":"46","author":"Huang","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.isci.2026.117168_bib32","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2022.111067","article-title":"Resolution of R-loops by topoisomerase III-beta (TOP3B) in coordination with the DEAD-box helicase DDX5","volume":"40","author":"Saha","year":"2022","journal-title":"Cell Rep."},{"key":"10.1016\/j.isci.2026.117168_bib33","doi-asserted-by":"crossref","first-page":"7974","DOI":"10.1073\/pnas.122007999","article-title":"Preferential cleavage of plasmid-based R-loops and D-loops by Drosophila topoisomerase IIIbeta","volume":"99","author":"Wilson-Sali","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.isci.2026.117168_bib34","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/j.molcel.2014.01.011","article-title":"Arginine Methylation Facilitates the Recruitment of TOP3B to Chromatin to Prevent R Loop Accumulation","volume":"53","author":"Yang","year":"2014","journal-title":"Mol. Cell"},{"key":"10.1016\/j.isci.2026.117168_bib35","doi-asserted-by":"crossref","first-page":"8573","DOI":"10.1093\/nar\/gkab642","article-title":"TDRD3 promotes DHX9 chromatin recruitment and R-loop resolution","volume":"49","author":"Yuan","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.isci.2026.117168_bib36","doi-asserted-by":"crossref","DOI":"10.1111\/acel.13554","article-title":"Proper control of R-loop homeostasis is required for maintenance of gene expression and neuronal function during aging","volume":"21","author":"Jauregui-Lozano","year":"2022","journal-title":"Aging Cell"},{"key":"10.1016\/j.isci.2026.117168_bib37","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1038\/s41467-025-55959-y","article-title":"Structural insights into human topoisomerase 3\u03b2 DNA and RNA catalysis and nucleic acid gate dynamics","volume":"16","author":"Yang","year":"2025","journal-title":"Nat. Commun."},{"key":"10.1016\/j.isci.2026.117168_bib38","doi-asserted-by":"crossref","DOI":"10.1016\/j.pneurobio.2024.102568","article-title":"Tdrd3-null mice show post-transcriptional and behavioral impairments associated with neurogenesis and synaptic plasticity","volume":"233","author":"Zhu","year":"2024","journal-title":"Prog. Neurobiol."},{"key":"10.1016\/j.isci.2026.117168_bib39","doi-asserted-by":"crossref","first-page":"2415","DOI":"10.1093\/nar\/gkad086","article-title":"A dual-activity topoisomerase complex promotes both transcriptional activation and repression in response to starvation","volume":"51","author":"Su","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.isci.2026.117168_bib40","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1038\/nrm.2016.111","article-title":"Roles of eukaryotic topoisomerases in transcription, replication and genomic stability","volume":"17","author":"Pommier","year":"2016","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.isci.2026.117168_bib41","doi-asserted-by":"crossref","first-page":"7013","DOI":"10.1093\/nar\/gkac538","article-title":"A dual-activity topoisomerase complex regulates mRNA translation and turnover","volume":"50","author":"Su","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.isci.2026.117168_bib42","doi-asserted-by":"crossref","first-page":"7524","DOI":"10.1038\/s41467-023-43151-z","article-title":"The TDRD3-USP9X complex and MIB1 regulate TOP3B homeostasis and prevent deleterious TOP3B cleavage complexes","volume":"14","author":"Saha","year":"2023","journal-title":"Nat. Commun."},{"key":"10.1016\/j.isci.2026.117168_bib43","doi-asserted-by":"crossref","first-page":"1734","DOI":"10.1038\/s41596-019-0159-1","article-title":"High-resolution, strand-specific R-loop mapping via S9.6-based DNA-RNA immunoprecipitation and high-throughput sequencing","volume":"14","author":"Sanz","year":"2019","journal-title":"Nat. Protoc."},{"key":"10.1016\/j.isci.2026.117168_bib44","first-page":"10","article-title":"Mapping R-Loops and RNA:DNA Hybrids with S9.6-Based Immunoprecipitation Methods","volume":"174","author":"Sanz","year":"2021","journal-title":"J. Vis. Exp."},{"key":"10.1016\/j.isci.2026.117168_bib45","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1038\/nrc2523","article-title":"GammaH2AX and cancer","volume":"8","author":"Bonner","year":"2008","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.isci.2026.117168_bib46","doi-asserted-by":"crossref","first-page":"1624","DOI":"10.1016\/j.humpath.2010.01.027","article-title":"Significance of topoisomerase IIIbeta expression in breast ductal carcinomas: strong associations with disease-specific survival and metastasis","volume":"41","author":"Oliveira-Costa","year":"2010","journal-title":"Hum. Pathol."},{"key":"10.1016\/j.isci.2026.117168_bib47","doi-asserted-by":"crossref","first-page":"124239","DOI":"10.1016\/j.eswa.2024.124239","article-title":"Discovering novel prognostic biomarkers of hepatocellular carcinoma using eXplainable Artificial Intelligence","volume":"252","author":"Gutierrez-Chakraborty","year":"2024","journal-title":"Expert Syst. Appl."},{"key":"10.1016\/j.isci.2026.117168_bib48","doi-asserted-by":"crossref","DOI":"10.1016\/j.gene.2020.144859","article-title":"Mining topoisomerase isoforms in gastric cancer","volume":"754","author":"Hou","year":"2020","journal-title":"Gene"},{"key":"10.1016\/j.isci.2026.117168_bib49","doi-asserted-by":"crossref","first-page":"3390","DOI":"10.1158\/0008-5472.CAN-08-2981","article-title":"Non-small cell lung cancer exhibits transcript overexpression of genes associated with homologous recombination and DNA replication pathways","volume":"69","author":"Saviozzi","year":"2009","journal-title":"Cancer Res."},{"key":"10.1016\/j.isci.2026.117168_bib50","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/j.trecan.2019.08.006","article-title":"R Loops and Their Composite Cancer Connections","volume":"5","author":"Wells","year":"2019","journal-title":"Trends Cancer"},{"key":"10.1016\/j.isci.2026.117168_bib51","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2021.105927","article-title":"Small molecule targeting topoisomerase 3beta for cancer therapy","volume":"174","author":"Zhang","year":"2021","journal-title":"Pharmacol. Res."},{"key":"10.1016\/j.isci.2026.117168_bib52","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1042\/EBC20200032","article-title":"Non-coding RNA in cancer","volume":"65","author":"Yan","year":"2021","journal-title":"Essays Biochem."},{"key":"10.1016\/j.isci.2026.117168_bib53","doi-asserted-by":"crossref","DOI":"10.3390\/cancers13061372","article-title":"Non-Coding RNAs in Cancer Diagnosis and Therapy: Focus on Lung Cancer","volume":"13","author":"Le","year":"2021","journal-title":"Cancers (Basel)"},{"key":"10.1016\/j.isci.2026.117168_bib54","doi-asserted-by":"crossref","DOI":"10.1016\/j.tranon.2023.101730","article-title":"Unlocking the potential of non-coding RNAs in cancer research and therapy","volume":"35","author":"Uppaluri","year":"2023","journal-title":"Transl. Oncol."},{"key":"10.1016\/j.isci.2026.117168_bib55","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1038\/s41576-024-00693-2","article-title":"Targeting and engineering long non-coding RNAs for cancer therapy","volume":"25","author":"Coan","year":"2024","journal-title":"Nat. Rev. Genet."},{"key":"10.1016\/j.isci.2026.117168_bib56","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1186\/s12943-020-01287-2","article-title":"Long noncoding RNAs: functions and mechanisms in colon cancer","volume":"19","author":"Chen","year":"2020","journal-title":"Mol. Cancer"},{"key":"10.1016\/j.isci.2026.117168_bib57","doi-asserted-by":"crossref","first-page":"3940","DOI":"10.1038\/s41467-020-17858-2","article-title":"Topoisomerase 1 prevents replication stress at R-loop-enriched transcription termination sites","volume":"11","author":"Promonet","year":"2020","journal-title":"Nat. Commun."},{"key":"10.1016\/j.isci.2026.117168_bib58","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1038\/nprot.2017.150","article-title":"Genome-wide mapping of endogenous G-quadruplex DNA structures by chromatin immunoprecipitation and high-throughput sequencing","volume":"13","author":"H\u00e4nsel-Hertsch","year":"2018","journal-title":"Nat. Protoc."},{"key":"10.1016\/j.isci.2026.117168_bib59","doi-asserted-by":"crossref","first-page":"e13","DOI":"10.1093\/nar\/gkab1073","article-title":"Genome-wide mapping of G-quadruplex structures with CUT&Tag","volume":"50","author":"Lyu","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.isci.2026.117168_bib60","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1073\/pnas.1810409116","article-title":"DNA damage and genome instability by G-quadruplex ligands are mediated by R loops in human cancer cells","volume":"116","author":"De Magis","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.isci.2026.117168_bib61","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/bs.mie.2024.01.008","article-title":"Immunofluorescence microscopy of G-quadruplexes and R-loops","volume":"695","author":"Miglietta","year":"2024","journal-title":"Methods Enzymol."},{"key":"10.1016\/j.isci.2026.117168_bib62","doi-asserted-by":"crossref","first-page":"11942","DOI":"10.1093\/nar\/gkaa944","article-title":"G-quadruplex-R-loop interactions and the mechanism of anticancer G-quadruplex binders","volume":"48","author":"Miglietta","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.isci.2026.117168_bib63","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1038\/nchem.1548","article-title":"Quantitative visualization of DNA G-quadruplex structures in human cells","volume":"5","author":"Biffi","year":"2013","journal-title":"Nat. Chem."},{"key":"10.1016\/j.isci.2026.117168_bib64","doi-asserted-by":"crossref","first-page":"2267","DOI":"10.1016\/j.molcel.2022.04.014","article-title":"Walking a tightrope: The complex balancing act of R-loops in genome stability","volume":"82","author":"Brickner","year":"2022","journal-title":"Mol. Cell"},{"key":"10.1016\/j.isci.2026.117168_bib65","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1016\/j.molcel.2014.10.020","article-title":"Transcription-coupled nucleotide excision repair factors promote R-loop-induced genome instability","volume":"56","author":"Sollier","year":"2014","journal-title":"Mol. Cell"},{"key":"10.1016\/j.isci.2026.117168_bib66","doi-asserted-by":"crossref","first-page":"3167","DOI":"10.1016\/j.celrep.2019.08.041","article-title":"Dual Processing of R-Loops and Topoisomerase I Induces Transcription-Dependent DNA Double-Strand Breaks","volume":"28","author":"Cristini","year":"2019","journal-title":"Cell Rep."},{"key":"10.1016\/j.isci.2026.117168_bib67","doi-asserted-by":"crossref","first-page":"8909","DOI":"10.1038\/ncomms9909","article-title":"Mutagenic consequences of a single G-quadruplex demonstrate mitotic inheritance of DNA replication fork barriers","volume":"6","author":"Lemmens","year":"2015","journal-title":"Nat. Commun."},{"key":"10.1016\/j.isci.2026.117168_bib68","doi-asserted-by":"crossref","first-page":"4033","DOI":"10.1038\/emboj.2011.316","article-title":"G-quadruplex-induced instability during leading-strand replication","volume":"30","author":"Lopes","year":"2011","journal-title":"EMBO J."},{"key":"10.1016\/j.isci.2026.117168_bib69","doi-asserted-by":"crossref","DOI":"10.3390\/biom11091284","article-title":"Impact of G-Quadruplexes on the Regulation of Genome Integrity, DNA Damage and Repair","volume":"11","author":"Pavlova","year":"2021","journal-title":"Biomolecules"},{"key":"10.1016\/j.isci.2026.117168_bib70","doi-asserted-by":"crossref","first-page":"2198","DOI":"10.1093\/nar\/gkae098","article-title":"G-quadruplex-mediated genomic instability drives SNVs in cancer","volume":"52","author":"Richl","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.isci.2026.117168_bib71","doi-asserted-by":"crossref","first-page":"4656","DOI":"10.1038\/s41467-022-32221-3","article-title":"Structural and biochemical basis for DNA and RNA catalysis by human Topoisomerase 3beta","volume":"13","author":"Yang","year":"2022","journal-title":"Nat. Commun."},{"key":"10.1016\/j.isci.2026.117168_bib72","doi-asserted-by":"crossref","first-page":"6260","DOI":"10.1073\/pnas.1819476116","article-title":"Interplay between DNA sequence and negative superhelicity drives R-loop structures","volume":"116","author":"Stolz","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.isci.2026.117168_bib73","article-title":"Genome-wide Mapping of Topoisomerase Binding Sites Suggests Topoisomerase 3alpha (TOP3A) as a Reader of Transcription-Replication Conflicts (TRC)","author":"Zhang","year":"2024","journal-title":"bioRxiv"},{"key":"10.1016\/j.isci.2026.117168_bib74","doi-asserted-by":"crossref","first-page":"3168","DOI":"10.1016\/j.jmb.2016.08.031","article-title":"R Loops and Links to Human Disease","volume":"429","author":"Richard","year":"2017","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.isci.2026.117168_bib75","article-title":"Attenuation of RNA polymerase II pausing mitigates BRCA1-associated R-loop accumulation and tumorigenesis","volume":"8","author":"Zhang","year":"2017","journal-title":"Nat. Commun."},{"key":"10.1016\/j.isci.2026.117168_bib76","doi-asserted-by":"crossref","first-page":"5086","DOI":"10.1093\/nar\/gkz262","article-title":"BRCA1-associated R-loop affects transcription and differentiation in breast luminal epithelial cells","volume":"47","author":"Chiang","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.isci.2026.117168_bib77","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1038\/s41580-022-00474-x","article-title":"Sources, resolution and physiological relevance of R-loops and RNA-DNA hybrids","volume":"23","author":"Petermann","year":"2022","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.isci.2026.117168_bib78","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1004630","article-title":"Out of balance: R-loops in human disease","volume":"10","author":"Groh","year":"2014","journal-title":"PLoS Genet."},{"key":"10.1016\/j.isci.2026.117168_bib79","doi-asserted-by":"crossref","DOI":"10.3390\/cancers15204986","article-title":"R-Loops in Genome Instability and Cancer","volume":"15","author":"Li","year":"2023","journal-title":"Cancers (Basel)"},{"key":"10.1016\/j.isci.2026.117168_bib80","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1016\/j.molcel.2019.10.002","article-title":"R-Loops Promote Antisense Transcription across the Mammalian Genome","volume":"76","author":"Tan-Wong","year":"2019","journal-title":"Mol. Cell"},{"key":"10.1016\/j.isci.2026.117168_bib81","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1016\/j.molcel.2022.01.014","article-title":"HOTTIP-dependent R-loop formation regulates CTCF boundary activity and TAD integrity in leukemia","volume":"82","author":"Luo","year":"2022","journal-title":"Mol. Cell"},{"key":"10.1016\/j.isci.2026.117168_bib82","article-title":"Clinical and Mechanistic Implications of R-Loops in Human Leukemias","volume":"24","author":"Lee","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.isci.2026.117168_bib83","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1101\/gr.158436.113","article-title":"GC skew at the 5' and 3' ends of human genes links R-loop formation to epigenetic regulation and transcription termination","volume":"23","author":"Ginno","year":"2013","journal-title":"Genome Res."},{"key":"10.1016\/j.isci.2026.117168_bib84","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/j.molcel.2017.10.008","article-title":"R-ChIP Using Inactive RNase H Reveals Dynamic Coupling of R-loops with Transcriptional Pausing at Gene Promoters","volume":"68","author":"Chen","year":"2017","journal-title":"Mol. Cell"},{"key":"10.1016\/j.isci.2026.117168_bib85","doi-asserted-by":"crossref","first-page":"12816","DOI":"10.1073\/pnas.1007580107","article-title":"Mechanisms and implications of transcription blockage by guanine-rich DNA sequences","volume":"107","author":"Belotserkovskii","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.isci.2026.117168_bib86","doi-asserted-by":"crossref","first-page":"6589","DOI":"10.1093\/nar\/gkx403","article-title":"Strong transcription blockage mediated by R-loop formation within a G-rich homopurine-homopyrimidine sequence localized in the vicinity of the promoter","volume":"45","author":"Belotserkovskii","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.isci.2026.117168_bib87","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1016\/j.molcel.2003.08.010","article-title":"Cotranscriptionally formed DNA:RNA hybrids mediate transcription elongation impairment and transcription-associated recombination","volume":"12","author":"Huertas","year":"2003","journal-title":"Mol. Cell"},{"key":"10.1016\/j.isci.2026.117168_bib88","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1101\/gad.1200804","article-title":"Intracellular transcription of G-rich DNAs induces formation of G-loops, novel structures containing G4 DNA","volume":"18","author":"Duquette","year":"2004","journal-title":"Genes Dev."},{"key":"10.1016\/j.isci.2026.117168_bib89","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1021\/ja4085572","article-title":"Mechanism and manipulation of DNA:RNA hybrid G-quadruplex formation in transcription of G-rich DNA","volume":"136","author":"Zhang","year":"2014","journal-title":"J. Am. Chem. Soc."},{"key":"10.1016\/j.isci.2026.117168_bib90","doi-asserted-by":"crossref","first-page":"7566","DOI":"10.1093\/nar\/gky554","article-title":"Toward predictive R-loop computational biology: genome-scale prediction of R-loops reveals their association with complex promoter structures, G-quadruplexes and transcriptionally active enhancers","volume":"46","author":"Kuznetsov","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.isci.2026.117168_bib91","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1038\/s41556-024-01437-4","article-title":"Intertwining roles of R-loops and G-quadruplexes in DNA repair, transcription and genome organization","volume":"26","author":"Wulfridge","year":"2024","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.isci.2026.117168_bib92","doi-asserted-by":"crossref","first-page":"2609","DOI":"10.1021\/acschembio.7b00435","article-title":"Superhelicity Constrains a Localized and R-Loop-Dependent Formation of G-Quadruplexes at the Upstream Region of Transcription","volume":"12","author":"Zheng","year":"2017","journal-title":"ACS Chem. Biol."},{"key":"10.1016\/j.isci.2026.117168_bib93","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1016\/j.cell.2011.04.015","article-title":"DNA replication through G-quadruplex motifs is promoted by the Saccharomyces cerevisiae Pif1 DNA helicase","volume":"145","author":"Paeschke","year":"2011","journal-title":"Cell"},{"key":"10.1016\/j.isci.2026.117168_bib94","doi-asserted-by":"crossref","first-page":"2586","DOI":"10.1158\/0008-5472.CAN-06-2419","article-title":"G-rich proto-oncogenes are targeted for genomic instability in B-cell lymphomas","volume":"67","author":"Duquette","year":"2007","journal-title":"Cancer Res."},{"key":"10.1016\/j.isci.2026.117168_bib95","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.molcel.2012.04.009","article-title":"R loops: from transcription byproducts to threats to genome stability","volume":"46","author":"Aguilera","year":"2012","journal-title":"Mol. Cell"},{"key":"10.1016\/j.isci.2026.117168_bib96","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1016\/j.cell.2019.08.055","article-title":"R Loops: From Physiological to Pathological Roles","volume":"179","author":"Garc\u00eda-Muse","year":"2019","journal-title":"Cell"},{"key":"10.1016\/j.isci.2026.117168_bib97","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1016\/j.cell.2017.07.043","article-title":"Transcription-Replication Conflict Orientation Modulates R-Loop Levels and Activates Distinct DNA Damage Responses","volume":"170","author":"Hamperl","year":"2017","journal-title":"Cell"},{"key":"10.1016\/j.isci.2026.117168_bib98","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1038\/embor.2009.97","article-title":"Ataxia telangiectasia mutated activation by transcription- and topoisomerase I-induced DNA double-strand breaks","volume":"10","author":"Sordet","year":"2009","journal-title":"EMBO Rep."},{"key":"10.1016\/j.isci.2026.117168_bib99","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.72286","article-title":"The interplay of RNA:DNA hybrid structure and G-quadruplexes determines the outcome of R-loop-replisome collisions","volume":"10","author":"Kumar","year":"2021","journal-title":"eLife"},{"key":"10.1016\/j.isci.2026.117168_bib100","article-title":"Identification and characterization of topoisomerase III beta poisons","volume":"120","author":"Wang","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.isci.2026.117168_bib104","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1021\/acs.jnatprod.5c00329","article-title":"Furanoheliangolides from Centratherum punctatum and a General Approach for Stereochemical Assignment of Flexible Chiral Side Chains","volume":"88","author":"Khong","year":"2025","journal-title":"J. Nat. Prod."},{"key":"10.1016\/j.isci.2026.117168_bib105","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: an open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"10.1016\/j.isci.2026.117168_bib106","doi-asserted-by":"crossref","DOI":"10.1093\/gigascience\/giab008","article-title":"Twelve years of SAMtools and BCFtools","volume":"10","author":"Danecek","year":"2021","journal-title":"GigaScience"},{"key":"10.1016\/j.isci.2026.117168_bib101","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s13072-020-00343-x","article-title":"BAMscale: quantification of next-generation sequencing peaks and generation of scaled coverage tracks","volume":"13","author":"Pongor","year":"2020","journal-title":"Epigenetics Chromatin"},{"key":"10.1016\/j.isci.2026.117168_bib102","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1007\/978-1-60327-409-8_18","article-title":"gamma-H2AX detection in peripheral blood lymphocytes, splenocytes, bone marrow, xenografts, and skin","volume":"682","author":"Redon","year":"2011","journal-title":"Methods Mol. Biol."},{"key":"10.1016\/j.isci.2026.117168_bib103","doi-asserted-by":"crossref","first-page":"14119","DOI":"10.3390\/ijms140714119","article-title":"Evaluation of the gamma-H2AX assay for radiation biodosimetry in a swine model","volume":"14","author":"Moroni","year":"2013","journal-title":"Int. J. Mol. Sci."}],"container-title":["iScience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2589004226025460?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2589004226025460?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T01:10:11Z","timestamp":1791594611000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2589004226025460"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":106,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["S2589004226025460"],"URL":"https:\/\/doi.org\/10.1016\/j.isci.2026.117168","relation":{},"ISSN":["2589-0042"],"issn-type":[{"value":"2589-0042","type":"print"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Genome-wide mapping reveals increased R-loops in topoisomerase III-beta-deficient human cells","name":"articletitle","label":"Article Title"},{"value":"iScience","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.isci.2026.117168","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"117168"}}