{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T22:29:25Z","timestamp":1792621765835,"version":"4.5.0"},"reference-count":90,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"vor","delay-in-days":37,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C309\/A11566"],"award-info":[{"award-number":["C309\/A11566"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C2739\/A22897"],"award-info":[{"award-number":["C2739\/A22897"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["212969\/Z\/18\/Z"],"award-info":[{"award-number":["212969\/Z\/18\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["094885\/Z\/10\/Z"],"award-info":[{"award-number":["094885\/Z\/10\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Oestrogen receptor (ER) activation leads to the formation of DNA double strand breaks (DSB), promoting genomic instability and tumour heterogeneity. The single-stranded DNA cytosine deaminase APOBEC3B (A3B) serves as a co-activator of ER and is implicated in inducing DSBs at transcriptional enhancers regulated by ER. Using whole-genome sequencing in an engineered cell model lacking base excision repair (BER) function, we demonstrate that A3B preferentially targets transcriptionally active regulatory regions in an R-loop-dependent manner. Strand-specific DNA:RNA immunoprecipitation sequencing (ssDRIP-seq) and ssDNA-associated protein immunoprecipitation sequencing (SPI-seq) confirm that A3B binds to and deaminates ssDNA within R-loops, a process facilitated by ER transactivation. Furthermore, BER-mediated processing of A3B-induced uracil bases contributes to the formation of R-loop-associated DSBs, which are essential for ER-regulated gene activation. These findings establish a role for A3B in R-loop homeostasis and transcriptional regulation, with implications for understanding ER-driven genomic instability and potential therapeutic targeting of A3B.<\/jats:p>","DOI":"10.1038\/s41467-026-69679-4","type":"journal-article","created":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T23:45:13Z","timestamp":1771371913000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["R-loop editing by DNA cytosine deaminase APOBEC3B modulates the activity of oestrogen receptor enhancers"],"prefix":"10.1038","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9188-6307","authenticated-orcid":false,"given":"Chi","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2494-843X","authenticated-orcid":false,"given":"Yu-jing","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7689-2146","authenticated-orcid":false,"given":"Bingjie","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyan","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaoxi","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8061-6678","authenticated-orcid":false,"given":"Alexia","family":"Hervieu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco P.","family":"Licciardello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos","family":"Mitsopoulos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bissan","family":"Al-Lazikani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcello","family":"Tortorici","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1262-9522","authenticated-orcid":false,"given":"Olivia W.","family":"Rossanese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1659-3034","authenticated-orcid":false,"given":"Paul","family":"Workman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9342-1290","authenticated-orcid":false,"given":"Paul A.","family":"Clarke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,18]]},"reference":[{"key":"69679_CR1","doi-asserted-by":"publisher","unstructured":"Orzolek, I., Sobieraj, J. & Domagala-Kulawik, J. Estrogens, cancer and immunity. Cancers 14, https:\/\/doi.org\/10.3390\/cancers14092265 (2022).","DOI":"10.3390\/cancers14092265"},{"key":"69679_CR2","first-page":"612","volume":"158","author":"JA Yang","year":"2017","unstructured":"Yang, J. A., Stires, H., Belden, W. J. & Roepke, T. A. The arcuate estrogen-regulated transcriptome: estrogen response element-dependent and -independent signaling of ERalpha in female mice. Endocrinology 158, 612\u2013626 (2017).","journal-title":"Endocrinology"},{"key":"69679_CR3","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1210\/er.2018-00087","volume":"39","author":"SC Hewitt","year":"2018","unstructured":"Hewitt, S. C. & Korach, K. S. Estrogen receptors: new directions in the new millennium. Endocr. Rev. 39, 664\u2013675 (2018).","journal-title":"Endocr. Rev."},{"key":"69679_CR4","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2020.188482","volume":"1875","author":"A Rajan","year":"2021","unstructured":"Rajan, A. et al. Deregulated estrogen receptor signaling and DNA damage response in breast tumorigenesis. Biochim. Biophys. Acta Rev. Cancer 1875, 188482 (2021).","journal-title":"Biochim. Biophys. Acta Rev. Cancer"},{"key":"69679_CR5","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1016\/j.celrep.2015.08.066","volume":"13","author":"M Periyasamy","year":"2015","unstructured":"Periyasamy, M. et al. APOBEC3B-Mediated cytidine deamination is required for estrogen receptor action in breast cancer. Cell Rep. 13, 108\u2013121 (2015).","journal-title":"Cell Rep."},{"key":"69679_CR6","doi-asserted-by":"publisher","unstructured":"Stork, C. T. et al. Co-transcriptional R-loops are the main cause of estrogen-induced DNA damage. Elife 5, https:\/\/doi.org\/10.7554\/eLife.17548 (2016).","DOI":"10.7554\/eLife.17548"},{"key":"69679_CR7","doi-asserted-by":"publisher","first-page":"18123","DOI":"10.1073\/pnas.0408273101","volume":"101","author":"JJ Li","year":"2004","unstructured":"Li, J. J. et al. Estrogen mediates Aurora-A overexpression, centrosome amplification, chromosomal instability, and breast cancer in female ACI rats. Proc. Natl. Acad. Sci. USA 101, 18123\u201318128 (2004).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"69679_CR8","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1016\/j.cell.2012.04.024","volume":"149","author":"S Nik-Zainal","year":"2012","unstructured":"Nik-Zainal, S. et al. Mutational processes molding the genomes of 21 breast cancers. Cell 149, 979\u2013993 (2012).","journal-title":"Cell"},{"key":"69679_CR9","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1038\/nature17676","volume":"534","author":"S Nik-Zainal","year":"2016","unstructured":"Nik-Zainal, S. et al. Landscape of somatic mutations in 560 breast cancer whole-genome sequences. Nature 534, 47\u201354 (2016).","journal-title":"Nature"},{"key":"69679_CR10","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1038\/nrm3350","volume":"13","author":"E Compe","year":"2012","unstructured":"Compe, E. & Egly, J. M. TFIIH: when transcription met DNA repair. Nat. Rev. Mol. Cell Biol. 13, 343\u2013354 (2012).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"69679_CR11","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1016\/j.tig.2012.06.004","volume":"28","author":"I Kamileri","year":"2012","unstructured":"Kamileri, I., Karakasilioti, I. & Garinis, G. A. Nucleotide excision repair: new tricks with old bricks. Trends Genet. 28, 566\u2013573 (2012).","journal-title":"Trends Genet."},{"key":"69679_CR12","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/j.molcel.2013.10.018","volume":"52","author":"YW Fong","year":"2013","unstructured":"Fong, Y. W., Cattoglio, C. & Tjian, R. The intertwined roles of transcription and repair proteins. Mol. Cell 52, 291\u2013302 (2013).","journal-title":"Mol. Cell"},{"key":"69679_CR13","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.dnarep.2016.05.013","volume":"44","author":"D Schuermann","year":"2016","unstructured":"Schuermann, D., Weber, A. R. & Schar, P. Active DNA demethylation by DNA repair: Facts and uncertainties. DNA Repair 44, 92\u2013102 (2016).","journal-title":"DNA Repair"},{"key":"69679_CR14","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.1038\/s12276-021-00656-1","volume":"53","author":"B Perillo","year":"2021","unstructured":"Perillo, B., Castoria, G. & Migliaccio, A. Exploiting the mechanism of estrogen-induced transcription to fight breast cancer. Exp. Mol. Med. 53, 1205\u20131206 (2021).","journal-title":"Exp. Mol. Med."},{"key":"69679_CR15","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1016\/j.cell.2014.12.023","volume":"160","author":"J Puc","year":"2015","unstructured":"Puc, J. et al. Ligand-dependent enhancer activation regulated by topoisomerase-I activity. Cell 160, 367\u2013380 (2015).","journal-title":"Cell"},{"key":"69679_CR16","doi-asserted-by":"publisher","first-page":"1798","DOI":"10.1126\/science.1127196","volume":"312","author":"BG Ju","year":"2006","unstructured":"Ju, B. G. et al. A topoisomerase IIbeta-mediated dsDNA break required for regulated transcription. Science 312, 1798\u20131802 (2006).","journal-title":"Science"},{"key":"69679_CR17","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2019.102700","volume":"83","author":"AM Green","year":"2019","unstructured":"Green, A. M. & Weitzman, M. D. The spectrum of APOBEC3 activity: From anti-viral agents to anti-cancer opportunities. DNA Repair 83, 102700 (2019).","journal-title":"DNA Repair"},{"key":"69679_CR18","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.virol.2015.03.012","volume":"479-480","author":"RS Harris","year":"2015","unstructured":"Harris, R. S. & Dudley, J. P. APOBECs and virus restriction. Virology 479-480, 131\u2013145 (2015).","journal-title":"Virology"},{"key":"69679_CR19","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1016\/j.molmed.2015.02.007","volume":"21","author":"S Henderson","year":"2015","unstructured":"Henderson, S. & Fenton, T. APOBEC3 genes: retroviral restriction factors to cancer drivers. Trends Mol. Med. 21, 274\u2013284 (2015).","journal-title":"Trends Mol. Med."},{"key":"69679_CR20","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1038\/nature11881","volume":"494","author":"MB Burns","year":"2013","unstructured":"Burns, M. B. et al. APOBEC3B is an enzymatic source of mutation in breast cancer. Nature 494, 366\u2013370 (2013).","journal-title":"Nature"},{"key":"69679_CR21","doi-asserted-by":"publisher","first-page":"2695","DOI":"10.1016\/j.jmb.2018.04.044","volume":"430","author":"DJ Salamango","year":"2018","unstructured":"Salamango, D. J. et al. APOBEC3B Nuclear localization requires two distinct N-terminal domain surfaces. J. Mol. Biol. 430, 2695\u20132708 (2018).","journal-title":"J. Mol. Biol."},{"key":"69679_CR22","doi-asserted-by":"publisher","first-page":"958","DOI":"10.1038\/s41588-020-0674-6","volume":"52","author":"D Mas-Ponte","year":"2020","unstructured":"Mas-Ponte, D. & Supek, F. DNA mismatch repair promotes APOBEC3-mediated diffuse hypermutation in human cancers. Nat. Genet. 52, 958\u2013968 (2020).","journal-title":"Nat. Genet."},{"key":"69679_CR23","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.00534","volume":"2","author":"BJ Taylor","year":"2013","unstructured":"Taylor, B. J. et al. DNA deaminases induce break-associated mutation showers with implication of APOBEC3B and 3A in breast cancer kataegis. Elife 2, e00534 (2013).","journal-title":"Elife"},{"key":"69679_CR24","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.1601737","volume":"2","author":"EK Law","year":"2016","unstructured":"Law, E. K. et al. The DNA cytosine deaminase APOBEC3B promotes tamoxifen resistance in ER-positive breast cancer. Sci. Adv. 2, e1601737 (2016).","journal-title":"Sci. Adv."},{"key":"69679_CR25","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1016\/j.cell.2019.08.055","volume":"179","author":"T Garcia-Muse","year":"2019","unstructured":"Garcia-Muse, T. & Aguilera, A. R Loops: from physiological to pathological roles. Cell 179, 604\u2013618 (2019).","journal-title":"Cell"},{"key":"69679_CR26","doi-asserted-by":"publisher","unstructured":"Gu, S., Bodai, Z., Cowan, Q. T. & Komor, A. C. Base editors: expanding the types of DNA damage products harnessed for genome editing. Gene Genome Ed. 1, https:\/\/doi.org\/10.1016\/j.ggedit.2021.100005 (2021).","DOI":"10.1016\/j.ggedit.2021.100005"},{"key":"69679_CR27","doi-asserted-by":"publisher","first-page":"1721","DOI":"10.1038\/s41588-023-01504-w","volume":"55","author":"JL McCann","year":"2023","unstructured":"McCann, J. L. et al. APOBEC3B regulates R-loops and promotes transcription-associated mutagenesis in cancer. Nat. Genet. 55, 1721\u20131734 (2023).","journal-title":"Nat. Genet."},{"key":"69679_CR28","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1038\/s41586-020-1943-3","volume":"578","author":"LB Alexandrov","year":"2020","unstructured":"Alexandrov, L. B. et al. The repertoire of mutational signatures in human cancer. Nature 578, 94\u2013101 (2020).","journal-title":"Nature"},{"key":"69679_CR29","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.dnarep.2014.03.028","volume":"19","author":"HE Krokan","year":"2014","unstructured":"Krokan, H. E. et al. Error-free versus mutagenic processing of genomic uracil-relevance to cancer. DNA Repair 19, 38\u201347 (2014).","journal-title":"DNA Repair"},{"key":"69679_CR30","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1038\/s41586-022-04972-y","volume":"607","author":"M Petljak","year":"2022","unstructured":"Petljak, M. et al. Mechanisms of APOBEC3 mutagenesis in human cancer cells. Nature 607, 799\u2013807 (2022).","journal-title":"Nature"},{"key":"69679_CR31","doi-asserted-by":"publisher","first-page":"e0155391","DOI":"10.1371\/journal.pone.0155391","volume":"11","author":"MK Akre","year":"2016","unstructured":"Akre, M. K. et al. Mutation processes in 293-based clones overexpressing the DNA cytosine deaminase APOBEC3B. PLoS ONE 11, e0155391 (2016).","journal-title":"PLoS ONE"},{"key":"69679_CR32","doi-asserted-by":"publisher","first-page":"1273","DOI":"10.1016\/j.celrep.2016.01.021","volume":"14","author":"JI Hoopes","year":"2016","unstructured":"Hoopes, J. I. et al. APOBEC3A and APOBEC3B Preferentially deaminate the lagging strand template during DNA replication. Cell Rep. 14, 1273\u20131282 (2016).","journal-title":"Cell Rep."},{"key":"69679_CR33","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1038\/bjc.2017.133","volume":"117","author":"J Nikkila","year":"2017","unstructured":"Nikkila, J. et al. Elevated APOBEC3B expression drives a kataegic-like mutation signature and replication stress-related therapeutic vulnerabilities in p53-defective cells. Br. J. Cancer 117, 113\u2013123 (2017).","journal-title":"Br. J. Cancer"},{"key":"69679_CR34","doi-asserted-by":"publisher","first-page":"9440","DOI":"10.1073\/pnas.1922472117","volume":"117","author":"Y Sui","year":"2020","unstructured":"Sui, Y. et al. Analysis of APOBEC-induced mutations in yeast strains with low levels of replicative DNA polymerases. Proc. Natl. Acad. Sci. USA 117, 9440\u20139450 (2020).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"69679_CR35","doi-asserted-by":"publisher","first-page":"22158","DOI":"10.1073\/pnas.1904024116","volume":"116","author":"AA Serebrenik","year":"2019","unstructured":"Serebrenik, A. A. et al. The deaminase APOBEC3B triggers the death of cells lacking uracil DNA glycosylase. Proc. Natl. Acad. Sci. USA 116, 22158\u201322163 (2019).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"69679_CR36","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-0974-4","volume":"17","author":"W McLaren","year":"2016","unstructured":"McLaren, W. et al. The ensembl variant effect predictor. Genome Biol. 17, 122 (2016).","journal-title":"Genome Biol."},{"key":"69679_CR37","doi-asserted-by":"publisher","first-page":"2478","DOI":"10.1038\/nprot.2017.124","volume":"12","author":"J Ernst","year":"2017","unstructured":"Ernst, J. & Kellis, M. Chromatin-state discovery and genome annotation with ChromHMM. Nat. Protoc. 12, 2478\u20132492 (2017).","journal-title":"Nat. Protoc."},{"key":"69679_CR38","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17176-7","volume":"11","author":"CY Lee","year":"2020","unstructured":"Lee, C. Y. et al. R-loop induced G-quadruplex in non-template promotes transcription by successive R-loop formation. Nat. Commun. 11, 3392 (2020).","journal-title":"Nat. Commun."},{"key":"69679_CR39","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1038\/s41477-017-0004-x","volume":"3","author":"W Xu","year":"2017","unstructured":"Xu, W. et al. The R-loop is a common chromatin feature of the Arabidopsis genome. Nat. Plants 3, 704\u2013714 (2017).","journal-title":"Nat. Plants"},{"key":"69679_CR40","doi-asserted-by":"publisher","first-page":"1891","DOI":"10.1016\/j.celrep.2018.04.025","volume":"23","author":"A Cristini","year":"2018","unstructured":"Cristini, A., Groh, M., Kristiansen, M. S. & Gromak, N. RNA\/DNA Hybrid interactome identifies DXH9 as a molecular player in transcriptional termination and R-loop-associated DNA damage. Cell Rep. 23, 1891\u20131905 (2018).","journal-title":"Cell Rep."},{"key":"69679_CR41","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1101\/gr.146357.112","volume":"23","author":"ZX Zhou","year":"2013","unstructured":"Zhou, Z. X. et al. Mapping genomic hotspots of DNA damage by a single-strand-DNA-compatible and strand-specific ChIP-seq method. Genome Res. 23, 705\u2013715 (2013).","journal-title":"Genome Res."},{"key":"69679_CR42","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8","volume":"15","author":"MI Love","year":"2014","unstructured":"Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).","journal-title":"Genome Biol."},{"key":"69679_CR43","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1038\/nmeth.3960","volume":"13","author":"SV Lensing","year":"2016","unstructured":"Lensing, S. V. et al. DSBCapture: in situ capture and sequencing of DNA breaks. Nat. Methods 13, 855\u2013857 (2016).","journal-title":"Nat. Methods"},{"key":"69679_CR44","unstructured":"Differential Binding Analysis of ChIP-Seq peak data (https:\/\/github.com\/aeron15\/DiffBind (2015)."},{"key":"69679_CR45","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1093\/carcin\/bgq255","volume":"32","author":"LM Williamson","year":"2011","unstructured":"Williamson, L. M. & Lees-Miller, S. P. Estrogen receptor alpha-mediated transcription induces cell cycle-dependent DNA double-strand breaks. Carcinogenesis 32, 279\u2013285 (2011).","journal-title":"Carcinogenesis"},{"key":"69679_CR46","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.molcel.2012.04.009","volume":"46","author":"A Aguilera","year":"2012","unstructured":"Aguilera, A. & Garcia-Muse, T. R loops: from transcription byproducts to threats to genome stability. Mol. Cell 46, 115\u2013124 (2012).","journal-title":"Mol. Cell"},{"key":"69679_CR47","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1016\/j.molcel.2014.10.020","volume":"56","author":"J Sollier","year":"2014","unstructured":"Sollier, J. et al. Transcription-coupled nucleotide excision repair factors promote R-loop-induced genome instability. Mol. Cell 56, 777\u2013785 (2014).","journal-title":"Mol. Cell"},{"key":"69679_CR48","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1038\/nbt.1630","volume":"28","author":"CY McLean","year":"2010","unstructured":"McLean, C. Y. et al. GREAT improves functional interpretation of cis-regulatory regions. Nat. Biotechnol. 28, 495\u2013501 (2010).","journal-title":"Nat. Biotechnol."},{"key":"69679_CR49","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/j.cels.2015.12.004","volume":"1","author":"A Liberzon","year":"2015","unstructured":"Liberzon, A. et al. The molecular signatures database (MSigDB) hallmark gene set collection. Cell Syst. 1, 417\u2013425 (2015).","journal-title":"Cell Syst."},{"key":"69679_CR50","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1038\/ng.2764","volume":"45","author":"N Cancer Genome Atlas Research","year":"2013","unstructured":"Cancer Genome Atlas Research, N. et al. The cancer genome atlas pan-cancer analysis project. Nat. Genet. 45, 1113\u20131120 (2013).","journal-title":"Nat. Genet."},{"key":"69679_CR51","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1016\/j.cell.2018.03.042","volume":"173","author":"C Hutter","year":"2018","unstructured":"Hutter, C. & Zenklusen, J. C. The cancer genome atlas: creating lasting value beyond its data. Cell 173, 283\u2013285 (2018).","journal-title":"Cell"},{"key":"69679_CR52","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1016\/j.tcb.2015.05.003","volume":"25","author":"J Sollier","year":"2015","unstructured":"Sollier, J. & Cimprich, K. A. Breaking bad: R-loops and genome integrity. Trends Cell Biol. 25, 514\u2013522 (2015).","journal-title":"Trends Cell Biol."},{"key":"69679_CR53","doi-asserted-by":"publisher","first-page":"3167","DOI":"10.1016\/j.celrep.2019.08.041","volume":"28","author":"A Cristini","year":"2019","unstructured":"Cristini, A. et al. Dual processing of R-Loops and topoisomerase I induces transcription-dependent DNA double-strand breaks. Cell Rep. 28, 3167\u20133181 (2019).","journal-title":"Cell Rep."},{"key":"69679_CR54","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adi2095","volume":"9","author":"G Chatzinikolaou","year":"2023","unstructured":"Chatzinikolaou, G. et al. XPF interacts with TOP2B for R-loop processing and DNA looping on actively transcribed genes. Sci. Adv. 9, eadi2095 (2023).","journal-title":"Sci. Adv."},{"key":"69679_CR55","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1038\/s41594-020-0446-0","volume":"27","author":"V Sartorelli","year":"2020","unstructured":"Sartorelli, V. & Lauberth, S. M. Enhancer RNAs are an important regulatory layer of the epigenome. Nat. Struct. Mol. Biol. 27, 521\u2013528 (2020).","journal-title":"Nat. Struct. Mol. Biol."},{"key":"69679_CR56","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1038\/s41586-024-08578-4","volume":"640","author":"J Liu","year":"2025","unstructured":"Liu, J. et al. Endogenous DNA damage at sites of terminated transcripts. Nature 640, 240\u2013248 (2025).","journal-title":"Nature"},{"key":"69679_CR57","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1093\/jnci\/djt018","volume":"105","author":"J Long","year":"2013","unstructured":"Long, J. et al. A common deletion in the APOBEC3 genes and breast cancer risk. J. Natl. Cancer Inst. 105, 573\u2013579 (2013).","journal-title":"J. Natl. Cancer Inst."},{"key":"69679_CR58","doi-asserted-by":"publisher","DOI":"10.1186\/s13058-016-0717-1","volume":"18","author":"WX Wen","year":"2016","unstructured":"Wen, W. X. et al. Germline APOBEC3B deletion is associated with breast cancer risk in an Asian multi-ethnic cohort and with immune cell presentation. Breast Cancer Res. 18, 56 (2016).","journal-title":"Breast Cancer Res."},{"key":"69679_CR59","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6129","volume":"5","author":"V Caval","year":"2014","unstructured":"Caval, V., Suspene, R., Shapira, M., Vartanian, J. P. & Wain-Hobson, S. A prevalent cancer susceptibility APOBEC3A hybrid allele bearing APOBEC3B 3\u2019UTR enhances chromosomal DNA damage. Nat. Commun. 5, 5129 (2014).","journal-title":"Nat. Commun."},{"key":"69679_CR60","doi-asserted-by":"publisher","first-page":"1030","DOI":"10.1093\/carcin\/bgaa002","volume":"41","author":"KI Udquim","year":"2020","unstructured":"Udquim, K. I., Zettelmeyer, C., Banday, A. R., Lin, S. H. & Prokunina-Olsson, L. APOBEC3B expression in breast cancer cell lines and tumors depends on the estrogen receptor status. Carcinogenesis 41, 1030\u20131037 (2020).","journal-title":"Carcinogenesis"},{"key":"69679_CR61","doi-asserted-by":"publisher","first-page":"3366","DOI":"10.1038\/s41388-024-03171-5","volume":"43","author":"C Zhang","year":"2024","unstructured":"Zhang, C. et al. Characterisation of APOBEC3B-Mediated RNA editing in breast cancer cells reveals regulatory roles of NEAT1 and MALAT1 lncRNAs. Oncogene 43, 3366\u20133377 (2024).","journal-title":"Oncogene"},{"key":"69679_CR62","doi-asserted-by":"publisher","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","volume":"25","author":"H Li","year":"2009","unstructured":"Li, H. & Durbin, R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25, 1754\u20131760 (2009).","journal-title":"Bioinformatics"},{"key":"69679_CR63","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1038\/ng.806","volume":"43","author":"MA DePristo","year":"2011","unstructured":"DePristo, M. A. et al. A framework for variation discovery and genotyping using next-generation DNA sequencing data. Nat. Genet. 43, 491\u2013498 (2011).","journal-title":"Nat. Genet."},{"key":"69679_CR64","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1038\/s41586-020-2308-7","volume":"581","author":"KJ Karczewski","year":"2020","unstructured":"Karczewski, K. J. et al. The mutational constraint spectrum quantified from variation in 141,456 humans. Nature 581, 434\u2013443 (2020).","journal-title":"Nature"},{"key":"69679_CR65","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1016\/j.ajhg.2013.08.008","volume":"93","author":"R Piskol","year":"2013","unstructured":"Piskol, R., Ramaswami, G. & Li, J. B. Reliable identification of genomic variants from RNA-seq data. Am. J. Hum. Genet. 93, 641\u2013651 (2013).","journal-title":"Am. J. Hum. Genet."},{"key":"69679_CR66","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-019-2597-8","volume":"20","author":"M Wang","year":"2019","unstructured":"Wang, M. & Kong, L. pblat: a multithread blat algorithm speeding up aligning sequences to genomes. BMC Bioinformatics 20, 28 (2019).","journal-title":"BMC Bioinformatics"},{"key":"69679_CR67","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1093\/bioinformatics\/btq033","volume":"26","author":"AR Quinlan","year":"2010","unstructured":"Quinlan, A. R. & Hall, I. M. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 26, 841\u2013842 (2010).","journal-title":"Bioinformatics"},{"key":"69679_CR68","doi-asserted-by":"publisher","unstructured":"Turner, S. D. qqman: an R package for visualizing GWAS results using Q-Q and manhattan plots. J. Open Source Softw. 3, https:\/\/doi.org\/10.21105\/joss.00731 (2018).","DOI":"10.21105\/joss.00731"},{"key":"69679_CR69","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1101\/gr.229102","volume":"12","author":"WJ Kent","year":"2002","unstructured":"Kent, W. J. et al. The human genome browser at UCSC. Genome Res. 12, 996\u20131006 (2002).","journal-title":"Genome Res."},{"key":"69679_CR70","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-018-0539-0","volume":"10","author":"F Blokzijl","year":"2018","unstructured":"Blokzijl, F., Janssen, R., van Boxtel, R. & Cuppen, E. MutationalPatterns: comprehensive genome-wide analysis of mutational processes. Genome Med. 10, 33 (2018).","journal-title":"Genome Med."},{"key":"69679_CR71","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-11-367","volume":"11","author":"R Gaujoux","year":"2010","unstructured":"Gaujoux, R. & Seoighe, C. A flexible R package for nonnegative matrix factorization. BMC Bioinform. 11, 367 (2010).","journal-title":"BMC Bioinform."},{"key":"69679_CR72","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-22445-0","volume":"12","author":"H Huang","year":"2021","unstructured":"Huang, H. et al. Defining super-enhancer landscape in triple-negative breast cancer by multiomic profiling. Nat. Commun. 12, 2242 (2021).","journal-title":"Nat. Commun."},{"key":"69679_CR73","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.1101\/gr.219394.116","volume":"27","author":"L Halasz","year":"2017","unstructured":"Halasz, L. et al. RNA-DNA hybrid (R-loop) immunoprecipitation mapping: an analytical workflow to evaluate inherent biases. Genome Res. 27, 1063\u20131073 (2017).","journal-title":"Genome Res."},{"key":"69679_CR74","doi-asserted-by":"publisher","first-page":"D119","DOI":"10.1093\/nar\/gkw1054","volume":"45","author":"P Jenjaroenpun","year":"2017","unstructured":"Jenjaroenpun, P., Wongsurawat, T., Sutheeworapong, S. & Kuznetsov, V. A. R-loopDB: a database for R-loop forming sequences (RLFS) and R-loops. Nucleic Acids Res. 45, D119\u2013D127 (2017).","journal-title":"Nucleic Acids Res."},{"key":"69679_CR75","doi-asserted-by":"publisher","first-page":"1746","DOI":"10.1093\/nar\/gkw006","volume":"44","author":"A Bedrat","year":"2016","unstructured":"Bedrat, A., Lacroix, L. & Mergny, J. L. Re-evaluation of G-quadruplex propensity with G4Hunter. Nucleic Acids Res. 44, 1746\u20131759 (2016).","journal-title":"Nucleic Acids Res."},{"key":"69679_CR76","doi-asserted-by":"publisher","first-page":"14","DOI":"10.12688\/wellcomeopenres.10004.1","volume":"1","author":"P Stempor","year":"2016","unstructured":"Stempor, P. & Ahringer, J. SeqPlots - Interactive software for exploratory data analyses, pattern discovery and visualization in genomics. Wellcome Open Res. 1, 14 (2016).","journal-title":"Wellcome Open Res."},{"key":"69679_CR77","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1038\/nbt.1754","volume":"29","author":"JT Robinson","year":"2011","unstructured":"Robinson, J. T. et al. Integrative genomics viewer. Nat. Biotechnol. 29, 24\u201326 (2011).","journal-title":"Nat. Biotechnol."},{"key":"69679_CR78","doi-asserted-by":"publisher","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","volume":"25","author":"H Li","year":"2009","unstructured":"Li, H. et al. The Sequence Alignment\/Map format and SAMtools. Bioinformatics 25, 2078\u20132079 (2009).","journal-title":"Bioinformatics"},{"key":"69679_CR79","doi-asserted-by":"publisher","first-page":"1728","DOI":"10.1038\/nprot.2012.101","volume":"7","author":"J Feng","year":"2012","unstructured":"Feng, J., Liu, T., Qin, B., Zhang, Y. & Liu, X. S. Identifying ChIP-seq enrichment using MACS. Nat. Protoc. 7, 1728\u20131740 (2012).","journal-title":"Nat. Protoc."},{"key":"69679_CR80","doi-asserted-by":"publisher","first-page":"2761","DOI":"10.1093\/bioinformatics\/btv293","volume":"31","author":"V Jalili","year":"2015","unstructured":"Jalili, V., Matteucci, M., Masseroli, M. & Morelli, M. J. Using combined evidence from replicates to evaluate ChIP-seq peaks. Bioinformatics 31, 2761\u20132769 (2015).","journal-title":"Bioinformatics"},{"key":"69679_CR81","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","volume":"26","author":"MD Robinson","year":"2010","unstructured":"Robinson, M. D., McCarthy, D. J. & Smyth, G. K. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26, 139\u2013140 (2010).","journal-title":"Bioinformatics"},{"key":"69679_CR82","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1038\/nature10730","volume":"481","author":"CS Ross-Innes","year":"2012","unstructured":"Ross-Innes, C. S. et al. Differential oestrogen receptor binding is associated with clinical outcome in breast cancer. Nature 481, 389\u2013393 (2012).","journal-title":"Nature"},{"key":"69679_CR83","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-11-165","volume":"11","author":"RC McLeay","year":"2010","unstructured":"McLeay, R. C. & Bailey, T. L. Motif Enrichment Analysis: a unified framework and an evaluation on ChIP data. BMC Bioinform. 11, 165 (2010).","journal-title":"BMC Bioinform."},{"key":"69679_CR84","doi-asserted-by":"publisher","first-page":"W39","DOI":"10.1093\/nar\/gkv416","volume":"43","author":"TL Bailey","year":"2015","unstructured":"Bailey, T. L., Johnson, J., Grant, C. E. & Noble, W. S. The MEME suite. Nucleic Acids Res. 43, W39\u2013W49 (2015).","journal-title":"Nucleic Acids Res."},{"key":"69679_CR85","doi-asserted-by":"publisher","first-page":"2847","DOI":"10.1093\/bioinformatics\/btw313","volume":"32","author":"Z Gu","year":"2016","unstructured":"Gu, Z., Eils, R. & Schlesner, M. Complex heatmaps reveal patterns and correlations in multidimensional genomic data. Bioinformatics 32, 2847\u20132849 (2016).","journal-title":"Bioinformatics"},{"key":"69679_CR86","doi-asserted-by":"publisher","first-page":"1760","DOI":"10.1101\/gr.135350.111","volume":"22","author":"J Harrow","year":"2012","unstructured":"Harrow, J. et al. GENCODE: the reference human genome annotation for The ENCODE Project. Genome Res. 22, 1760\u20131774 (2012).","journal-title":"Genome Res."},{"key":"69679_CR87","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","volume":"29","author":"A Dobin","year":"2013","unstructured":"Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15\u201321 (2013).","journal-title":"Bioinformatics"},{"key":"69679_CR88","doi-asserted-by":"publisher","first-page":"e47","DOI":"10.1093\/nar\/gkz114","volume":"47","author":"Y Liao","year":"2019","unstructured":"Liao, Y., Smyth, G. K. & Shi, W. The R package Rsubread is easier, faster, cheaper and better for alignment and quantification of RNA sequencing reads. Nucleic Acids Res. 47, e47 (2019).","journal-title":"Nucleic Acids Res."},{"key":"69679_CR89","doi-asserted-by":"publisher","first-page":"15545","DOI":"10.1073\/pnas.0506580102","volume":"102","author":"A Subramanian","year":"2005","unstructured":"Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl. Acad. Sci. USA 102, 15545\u201315550 (2005).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"69679_CR90","doi-asserted-by":"publisher","DOI":"10.1002\/slct.202201456","volume":"7","author":"Y Zhang","year":"2022","unstructured":"Zhang, Y. et al. Discovery of APOBEC cytidine deaminases inhibitors using a BspH1 restriction enzyme-based biosensor. ChemistrySelect 7, e202201456 (2022).","journal-title":"ChemistrySelect"}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41467-026-69679-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-026-69679-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-026-69679-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T16:01:45Z","timestamp":1774627305000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41467-026-69679-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,18]]},"references-count":90,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["69679"],"URL":"https:\/\/doi.org\/10.1038\/s41467-026-69679-4","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,18]]},"assertion":[{"value":"20 March 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 February 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 February 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"C.Z., A.H., M.P.L., O.W.R., P.A.C., K.M., M.T., and P.W. are current or past employees of The Institute of Cancer Research, which has a commercial interest in a range of drug targets and operates a Rewards to Discoverers scheme, including A3B inhibitors, through which employees may receive financial benefits following the commercial licensing of a project. P.W. is an independent director at Storm Therapeutics, is a consultant\/advisory board member at Astex Pharmaceuticals, CV6 Therapeutics, Black Diamond Therapeutics, Vividion Therapeutics and Nextechinvest; reports receiving a commercial research grant from Sixth Element Capital, Astex Pharmaceuticals, and Merck; has ownership interest in Storm Therapeutics, Chroma Therapeutics, and Nextechinvest; and has an unpaid consultant\/advisory board relationship with the Chemical Probes Portal. The remaining authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"2887"}}