{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T23:33:23Z","timestamp":1791502403837,"version":"4.3.4"},"reference-count":95,"publisher":"Elsevier BV","issue":"18","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":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"US Department of Defense","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association Inc","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000957","name":"Alzheimer's Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000952","name":"Paul G Allen Family Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000952","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Cell"],"published-print":{"date-parts":[[2026,9]]},"DOI":"10.1016\/j.cell.2026.06.013","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T14:40:57Z","timestamp":1782916857000},"page":"5766-5782.e10","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":6,"title":["Recurrent patterns of TOP1-mediated neuronal genomic damage shared by major neurodegenerative disorders"],"prefix":"10.1016","volume":"189","author":[{"given":"Zinan","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lovelace J.","family":"Luquette","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanlan","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junho","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayoung","family":"Ku","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kisong","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nandini","family":"Ramesh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyun","family":"Bae","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Caplin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane D.","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bezawit","family":"Sahile","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kow","family":"Essuman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eitan","family":"Goodman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael B.","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"August Yue","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William J.","family":"Nathan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre","family":"Nussenzweig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clotilde","family":"Lagier-Tourenne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunjung Alice","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0156-2238","authenticated-orcid":false,"given":"Christopher A.","family":"Walsh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.cell.2026.06.013_bib1","doi-asserted-by":"crossref","first-page":"R105","DOI":"10.1093\/hmg\/ddx247","article-title":"Ageing as a risk factor for ALS\/FTD","volume":"26","author":"Niccoli","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.cell.2026.06.013_bib2","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1001\/jama.1995.03520410048025","article-title":"Age-specific incidence of Alzheimer's disease in a community population","volume":"273","author":"Hebert","year":"1995","journal-title":"JAMA"},{"key":"10.1016\/j.cell.2026.06.013_bib3","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.neuron.2013.07.033","article-title":"Converging mechanisms in ALS and FTD: disrupted RNA and protein homeostasis","volume":"79","author":"Ling","year":"2013","journal-title":"Neuron"},{"key":"10.1016\/j.cell.2026.06.013_bib4","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.neuron.2011.09.011","article-title":"Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS","volume":"72","author":"DeJesus-Hernandez","year":"2011","journal-title":"Neuron"},{"key":"10.1016\/j.cell.2026.06.013_bib5","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.neuron.2011.09.010","article-title":"A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD","volume":"72","author":"Renton","year":"2011","journal-title":"Neuron"},{"key":"10.1016\/j.cell.2026.06.013_bib6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jalz.2011.10.007","article-title":"National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease","volume":"8","author":"Hyman","year":"2012","journal-title":"Alzheimers Dement."},{"key":"10.1016\/j.cell.2026.06.013_bib7","doi-asserted-by":"crossref","first-page":"2064","DOI":"10.1046\/j.1471-4159.1997.69052064.x","article-title":"Evidence of increased oxidative damage in both sporadic and familial amyotrophic lateral sclerosis","volume":"69","author":"Ferrante","year":"1997","journal-title":"J. Neurochem."},{"key":"10.1016\/j.cell.2026.06.013_bib8","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1038\/nature13124","article-title":"C9orf72 nucleotide repeat structures initiate molecular cascades of disease","volume":"507","author":"Haeusler","year":"2014","journal-title":"Nature"},{"key":"10.1016\/j.cell.2026.06.013_bib9","doi-asserted-by":"crossref","first-page":"4696","DOI":"10.1073\/pnas.1818415116","article-title":"Motor neuron disease-associated loss of nuclear TDP-43 is linked to DNA double-strand break repair defects","volume":"116","author":"Mitra","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"10.1016\/j.cell.2026.06.013_bib10","doi-asserted-by":"crossref","first-page":"10540","DOI":"10.1073\/pnas.88.23.10540","article-title":"Excess brain protein oxidation and enzyme dysfunction in normal aging and in Alzheimer disease","volume":"88","author":"Smith","year":"1991","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"10.1016\/j.cell.2026.06.013_bib11","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/S0006-8993(99)02004-1","article-title":"DNA strand breaks in Alzheimer's disease","volume":"849","author":"Adamec","year":"1999","journal-title":"Brain Res."},{"key":"10.1016\/j.cell.2026.06.013_bib12","doi-asserted-by":"crossref","first-page":"2034","DOI":"10.1046\/j.1471-4159.1998.71052034.x","article-title":"Increased nuclear DNA oxidation in the brain in Alzheimer's disease","volume":"71","author":"Gabbita","year":"1998","journal-title":"J. Neurochem."},{"key":"10.1016\/j.cell.2026.06.013_bib13","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1126\/science.aao4426","article-title":"Aging and neurodegeneration are associated with increased mutations in single human neurons","volume":"359","author":"Lodato","year":"2018","journal-title":"Science"},{"key":"10.1016\/j.cell.2026.06.013_bib14","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1038\/s41586-022-04640-1","article-title":"Somatic genomic changes in single Alzheimer's disease neurons","volume":"604","author":"Miller","year":"2022","journal-title":"Nature"},{"key":"10.1016\/j.cell.2026.06.013_bib15","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1111\/j.1471-4159.2005.03615.x","article-title":"Increased oxidative damage in nuclear and mitochondrial DNA in mild cognitive impairment","volume":"96","author":"Wang","year":"2006","journal-title":"J. Neurochem."},{"key":"10.1016\/j.cell.2026.06.013_bib16","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.neuron.2016.09.015","article-title":"Poly(GR) in C9ORF72-Related ALS\/FTD Compromises Mitochondrial Function and Increases Oxidative Stress and DNA Damage in iPSC-Derived Motor Neurons","volume":"92","author":"Lopez-Gonzalez","year":"2016","journal-title":"Neuron"},{"key":"10.1016\/j.cell.2026.06.013_bib17","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/362059a0","article-title":"Mutations in Cu\/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis","volume":"362","author":"Rosen","year":"1993","journal-title":"Nature"},{"key":"10.1016\/j.cell.2026.06.013_bib18","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1038\/nsmb.2188","article-title":"The AAA-ATPase VCP\/p97 promotes 53BP1 recruitment by removing L3MBTL1 from DNA double-strand breaks","volume":"18","author":"Acs","year":"2011","journal-title":"Nat. Struct. Mol. Biol."},{"key":"10.1016\/j.cell.2026.06.013_bib19","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1038\/ncb2367","article-title":"The ubiquitin-selective segregase VCP\/p97 orchestrates the response to DNA double-strand breaks","volume":"13","author":"Meerang","year":"2011","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.cell.2026.06.013_bib20","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1038\/nn.3514","article-title":"Interaction of FUS and HDAC1 regulates DNA damage response and repair in neurons","volume":"16","author":"Wang","year":"2013","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.cell.2026.06.013_bib21","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1080\/15548627.2016.1210368","article-title":"SQSTM1\/p62 mediates crosstalk between autophagy and the UPS in DNA repair","volume":"12","author":"Hewitt","year":"2016","journal-title":"Autophagy"},{"key":"10.1016\/j.cell.2026.06.013_bib22","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.scr.2018.06.005","article-title":"NEK1 loss-of-function mutation induces DNA damage accumulation in ALS patient-derived motoneurons","volume":"30","author":"Higelin","year":"2018","journal-title":"Stem Cell Res."},{"key":"10.1016\/j.cell.2026.06.013_bib23","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-018-02894-w","article-title":"Senataxin resolves RNA:DNA hybrids forming at DNA double-strand breaks to prevent translocations","volume":"9","author":"Cohen","year":"2018","journal-title":"Nat. Commun."},{"key":"10.1016\/j.cell.2026.06.013_bib24","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1016\/j.cell.2020.12.025","article-title":"p53 is a central regulator driving neurodegeneration caused by C9orf72 poly(PR)","volume":"184","author":"Maor-Nof","year":"2021","journal-title":"Cell"},{"key":"10.1016\/j.cell.2026.06.013_bib25","doi-asserted-by":"crossref","DOI":"10.1093\/narmme\/ugae019","article-title":"C9orf72 repeat expansion creates the unstable folate-sensitive fragile site FRA9A","volume":"1","author":"Mirceta","year":"2024","journal-title":"NAR Mol. Med."},{"key":"10.1016\/j.cell.2026.06.013_bib26","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1038\/s41588-022-01180-2","article-title":"Single-cell genome sequencing of human neurons identifies somatic point mutation and indel enrichment in regulatory elements","volume":"54","author":"Luquette","year":"2022","journal-title":"Nat. Genet."},{"key":"10.1016\/j.cell.2026.06.013_bib27","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1016\/j.celrep.2019.04.003","article-title":"Loss of Nuclear TDP-43 Is Associated with Decondensation of LINE Retrotransposons","volume":"27","author":"Liu","year":"2019","journal-title":"Cell Rep."},{"key":"10.1016\/j.cell.2026.06.013_bib28","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1038\/s41586-022-04424-7","article-title":"TDP-43 represses cryptic exon inclusion in the FTD-ALS gene UNC13A","volume":"603","author":"Ma","year":"2022","journal-title":"Nature"},{"key":"10.1016\/j.cell.2026.06.013_bib29","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1007\/s00401-023-02599-5","article-title":"Cryptic exon detection and transcriptomic changes revealed in single-nuclei RNA sequencing of C9ORF72 patients spanning the ALS-FTD spectrum","volume":"146","author":"Gittings","year":"2023","journal-title":"Acta Neuropathol."},{"key":"10.1016\/j.cell.2026.06.013_bib30","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1126\/science.aab0983","article-title":"TDP-43 repression of nonconserved cryptic exons is compromised in ALS-FTD","volume":"349","author":"Ling","year":"2015","journal-title":"Science"},{"key":"10.1016\/j.cell.2026.06.013_bib31","doi-asserted-by":"crossref","DOI":"10.1186\/s40478-020-00961-2","article-title":"Quantitative patterns of motor cortex proteinopathy across ALS genotypes","volume":"8","author":"Nolan","year":"2020","journal-title":"Acta Neuropathol. Commun."},{"key":"10.1016\/j.cell.2026.06.013_bib32","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1001\/jamaneurol.2013.234","article-title":"An imbalance between excitatory and inhibitory neurotransmitters in amyotrophic lateral sclerosis revealed by use of 3-T proton magnetic resonance spectroscopy","volume":"70","author":"Foerster","year":"2013","journal-title":"JAMA Neurol."},{"key":"10.1016\/j.cell.2026.06.013_bib33","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1093\/brain\/awaa034","article-title":"Cortical interneuron-mediated inhibition delays the onset of amyotrophic lateral sclerosis","volume":"143","author":"Khademullah","year":"2020","journal-title":"Brain"},{"key":"10.1016\/j.cell.2026.06.013_bib34","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-021-23224-7","article-title":"Locomotor deficits in a mouse model of ALS are paralleled by loss of V1-interneuron connections onto fast motor neurons","volume":"12","author":"Allodi","year":"2021","journal-title":"Nat. Commun."},{"key":"10.1016\/j.cell.2026.06.013_bib35","doi-asserted-by":"crossref","first-page":"1955","DOI":"10.1016\/j.cell.2024.02.025","article-title":"Contrasting somatic mutation patterns in aging human neurons and oligodendrocytes","volume":"187","author":"Ganz","year":"2024","journal-title":"Cell"},{"key":"10.1016\/j.cell.2026.06.013_bib36","series-title":"Affymetrix\u00ae White Paper: Median of the Absolute Values of All Pairwise Differences and Quality Control on the Affymetrix Genome-Wide Human SNP Array 6.0","year":"2008"},{"key":"10.1016\/j.cell.2026.06.013_bib37","first-page":"227","article-title":"De la sclerose laterale amyotrophique. Symptomatologie","volume":"2","author":"Charcot","year":"1880","journal-title":"Lecons sur les Maladies du Systeme Nerveux Faites a La Salpetriere, 3rd ed.,"},{"key":"10.1016\/j.cell.2026.06.013_bib38","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.celrep.2012.12.008","article-title":"Deciphering signatures of mutational processes operative in human cancer","volume":"3","author":"Alexandrov","year":"2013","journal-title":"Cell Rep."},{"key":"10.1016\/j.cell.2026.06.013_bib39","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1016\/j.cell.2019.02.012","article-title":"Characterizing Mutational Signatures in Human Cancer Cell Lines Reveals Episodic APOBEC Mutagenesis","volume":"176","author":"Petljak","year":"2019","journal-title":"Cell"},{"key":"10.1016\/j.cell.2026.06.013_bib40","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/S1097-2765(00)80172-0","article-title":"Base excision repair of oxidative DNA damage activated by XPG protein","volume":"3","author":"Klungland","year":"1999","journal-title":"Mol. Cell"},{"key":"10.1016\/j.cell.2026.06.013_bib41","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/s41586-022-04403-y","article-title":"Signatures of TOP1 transcription-associated mutagenesis in cancer and germline","volume":"602","author":"Reijns","year":"2022","journal-title":"Nature"},{"key":"10.1016\/j.cell.2026.06.013_bib42","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1038\/s41586-020-1943-3","article-title":"The repertoire of mutational signatures in human cancer","volume":"578","author":"Alexandrov","year":"2020","journal-title":"Nature"},{"key":"10.1016\/j.cell.2026.06.013_bib43","doi-asserted-by":"crossref","first-page":"5157","DOI":"10.1093\/nar\/21.22.5157","article-title":"Induction of cleavage in topoisomerase I c-DNA by topoisomerase I enzymes from calf thymus and wheat germ in the presence and absence of camptothecin","volume":"21","author":"Tanizawa","year":"1993","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.cell.2026.06.013_bib44","doi-asserted-by":"crossref","first-page":"e104","DOI":"10.1093\/nar\/gkt171","article-title":"A rapid and sensitive assay for DNA-protein covalent complexes in living cells","volume":"41","author":"Kiianitsa","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.cell.2026.06.013_bib45","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.cell.2026.06.013_bib46","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1038\/nature14248","article-title":"Integrative analysis of 111 reference human epigenomes","volume":"518","author":"Roadmap Epigenomics","year":"2015","journal-title":"Nature"},{"key":"10.1016\/j.cell.2026.06.013_bib47","doi-asserted-by":"crossref","first-page":"2478","DOI":"10.1038\/nprot.2017.124","article-title":"Chromatin-state discovery and genome annotation with ChromHMM","volume":"12","author":"Ernst","year":"2017","journal-title":"Nat. Protoc."},{"key":"10.1016\/j.cell.2026.06.013_bib48","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1126\/science.aay0793","article-title":"Brain cell type-specific enhancer-promoter interactome maps and disease-risk association","volume":"366","author":"Nott","year":"2019","journal-title":"Science"},{"key":"10.1016\/j.cell.2026.06.013_bib49","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2013106118","article-title":"Accurate SNV detection in single cells by transposon-based whole-genome amplification of complementary strands","volume":"118","author":"Xing","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"10.1016\/j.cell.2026.06.013_bib50","article-title":"Divergent somatic mutation patterns among human cerebellar neuron types","author":"Gro\u0144ska-P\u0119ski","year":"2025","journal-title":"bioRxiv"},{"key":"10.1016\/j.cell.2026.06.013_bib51","article-title":"Somatic mutation in human cerebellum illustrates neuron type-specific patterns of age-related mutation","author":"Essuman","year":"2026","journal-title":"bioRxiv"},{"key":"10.1016\/j.cell.2026.06.013_bib52","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/j.tibs.2016.02.005","article-title":"The Balancing Act of Ribonucleotides in DNA","volume":"41","author":"Cerritelli","year":"2016","journal-title":"Trends Biochem. Sci."},{"key":"10.1016\/j.cell.2026.06.013_bib53","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms10805","article-title":"Impact of ribonucleotide incorporation by DNA polymerases beta and lambda on oxidative base excision repair","volume":"7","author":"Crespan","year":"2016","journal-title":"Nat. Commun."},{"key":"10.1016\/j.cell.2026.06.013_bib54","doi-asserted-by":"crossref","first-page":"8516","DOI":"10.1074\/jbc.274.13.8516","article-title":"Induction of reversible complexes between eukaryotic DNA topoisomerase I and DNA-containing oxidative base damages. 7, 8-dihydro-8-oxoguanine and 5-hydroxycytosine","volume":"274","author":"Pourquier","year":"1999","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.cell.2026.06.013_bib55","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.cell.2026.06.013_bib56","doi-asserted-by":"crossref","DOI":"10.3389\/fnagi.2021.751742","article-title":"Topoisomerase-Mediated DNA Damage in Neurological Disorders","volume":"13","author":"Crewe","year":"2021","journal-title":"Front. Aging Neurosci."},{"key":"10.1016\/j.cell.2026.06.013_bib57","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1038\/s41586-025-09435-8","article-title":"Single-cell transcriptomic and genomic changes in the ageing human brain","volume":"646","author":"Jeffries","year":"2025","journal-title":"Nature"},{"key":"10.1016\/j.cell.2026.06.013_bib58","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1038\/s41588-021-01001-y","article-title":"The threat of programmed DNA damage to neuronal genome integrity and plasticity","volume":"54","author":"Caldecott","year":"2022","journal-title":"Nat. Genet."},{"key":"10.1016\/j.cell.2026.06.013_bib59","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1038\/nature12504","article-title":"Topoisomerases facilitate transcription of long genes linked to autism","volume":"501","author":"King","year":"2013","journal-title":"Nature"},{"key":"10.1016\/j.cell.2026.06.013_bib60","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.neuron.2015.03.059","article-title":"Gene length matters in neurons","volume":"86","author":"Zylka","year":"2015","journal-title":"Neuron"},{"key":"10.1016\/j.cell.2026.06.013_bib61","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-020-15794-9","article-title":"Deletion of Topoisomerase 1 in excitatory neurons causes genomic instability and early onset neurodegeneration","volume":"11","author":"Fragola","year":"2020","journal-title":"Nat. Commun."},{"key":"10.1016\/j.cell.2026.06.013_bib62","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-020-15000-w","article-title":"TEX264 coordinates p97- and SPRTN-mediated resolution of topoisomerase 1-DNA adducts","volume":"11","author":"Fielden","year":"2020","journal-title":"Nat. Commun."},{"key":"10.1016\/j.cell.2026.06.013_bib63","doi-asserted-by":"crossref","first-page":"5698","DOI":"10.1016\/j.cell.2024.08.020","article-title":"TEX264 drives selective autophagy of DNA lesions to promote DNA repair and cell survival","volume":"187","author":"Lascaux","year":"2024","journal-title":"Cell"},{"key":"10.1016\/j.cell.2026.06.013_bib64","doi-asserted-by":"crossref","DOI":"10.1126\/science.adu1351","article-title":"Diverse somatic genomic alterations in single neurons in chronic traumatic encephalopathy","volume":"390","author":"Dong","year":"2025","journal-title":"Science"},{"key":"10.1016\/j.cell.2026.06.013_bib65","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1111\/bpa.12248","article-title":"The neuropathology of chronic traumatic encephalopathy","volume":"25","author":"McKee","year":"2015","journal-title":"Brain Pathol."},{"key":"10.1016\/j.cell.2026.06.013_bib66","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1007\/s00401-013-1211-9","article-title":"Staging TDP-43 pathology in Alzheimer's disease","volume":"127","author":"Josephs","year":"2014","journal-title":"Acta Neuropathol."},{"key":"10.1016\/j.cell.2026.06.013_bib67","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1097\/NEN.0b013e3181ee7d85","article-title":"TDP-43 proteinopathy and motor neuron disease in chronic traumatic encephalopathy","volume":"69","author":"McKee","year":"2010","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"10.1016\/j.cell.2026.06.013_bib68","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.pneurobio.2017.08.003","article-title":"Chronic traumatic encephalopathy-integration of canonical traumatic brain injury secondary injury mechanisms with tau pathology","volume":"158","author":"Kulbe","year":"2017","journal-title":"Prog. Neurobiol."},{"key":"10.1016\/j.cell.2026.06.013_bib69","doi-asserted-by":"crossref","DOI":"10.1038\/s42003-022-04369-7","article-title":"RNaseH2A downregulation drives inflammatory gene expression via genomic DNA fragmentation in senescent and cancer cells","volume":"5","author":"Sugawara","year":"2022","journal-title":"Commun. Biol."},{"key":"10.1016\/j.cell.2026.06.013_bib70","article-title":"Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets","volume":"8","author":"Gao","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"10.1016\/j.cell.2026.06.013_bib71","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1038\/ng1842","article-title":"Mutations in genes encoding ribonuclease H2 subunits cause Aicardi-Gouti\u00e8res syndrome and mimic congenital viral brain infection","volume":"38","author":"Crow","year":"2006","journal-title":"Nat. Genet."},{"key":"10.1016\/j.cell.2026.06.013_bib72","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1038\/nn.3715","article-title":"Aberrant topoisomerase-1 DNA lesions are pathogenic in neurodegenerative genome instability syndromes","volume":"17","author":"Katyal","year":"2014","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.cell.2026.06.013_bib73","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.dnarep.2015.04.019","article-title":"The Repeat Expansion Diseases: The dark side of DNA repair","volume":"32","author":"Zhao","year":"2015","journal-title":"DNA Repair (Amst)"},{"key":"10.1016\/j.cell.2026.06.013_bib74","article-title":"CROPseq-multi: a universal solution for multiplexed perturbation in high-content pooled CRISPR screens","author":"Walton","year":"2025","journal-title":"bioRxiv"},{"key":"10.1016\/j.cell.2026.06.013_bib75","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.cell.2012.09.035","article-title":"Single-neuron sequencing analysis of L1 retrotransposition and somatic mutation in the human brain","volume":"151","author":"Evrony","year":"2012","journal-title":"Cell"},{"key":"10.1016\/j.cell.2026.06.013_bib76","doi-asserted-by":"crossref","DOI":"10.1186\/s12864-019-6041-2","article-title":"SigProfilerMatrixGenerator: a tool for visualizing and exploring patterns of small mutational events","volume":"20","author":"Bergstrom","year":"2019","journal-title":"BMC Genomics"},{"key":"10.1016\/j.cell.2026.06.013_bib77","article-title":"Uncovering novel mutational signatures by de novo extraction with SigProfilerExtractor","volume":"2","author":"Islam","year":"2022","journal-title":"Cell Genom."},{"key":"10.1016\/j.cell.2026.06.013_bib78","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1126\/science.aaz1776","article-title":"The GTEx Consortium atlas of genetic regulatory effects across human tissues","volume":"369","year":"2020","journal-title":"Science"},{"key":"10.1016\/j.cell.2026.06.013_bib79","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-023-37266-6","article-title":"Integrated analysis of genomic and transcriptomic data for the discovery of splice-associated variants in cancer","volume":"14","author":"Cotto","year":"2023","journal-title":"Nat. Commun."},{"key":"10.1016\/j.cell.2026.06.013_bib80","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/s41588-017-0004-9","article-title":"Annotation-free quantification of RNA splicing using LeafCutter","volume":"50","author":"Li","year":"2018","journal-title":"Nat. Genet."},{"key":"10.1016\/j.cell.2026.06.013_bib81","article-title":"Aligning Sequence Reads, Clone Sequences and Assembly Contigs with BWA-MEM.","author":"Li","year":"2013","journal-title":"arXiv"},{"key":"10.1016\/j.cell.2026.06.013_bib82","doi-asserted-by":"crossref","DOI":"10.1093\/bioinformatics\/btag205","article-title":"Duplex-Indel: a snakemake pipeline for somatic indel calling in Tn5 transposase-based duplex sequencing data","volume":"42","author":"Dong","year":"2026","journal-title":"Bioinformatics"},{"key":"10.1016\/j.cell.2026.06.013_bib83","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms14049","article-title":"Massively parallel digital transcriptional profiling of single cells","volume":"8","author":"Zheng","year":"2017","journal-title":"Nat. Commun."},{"key":"10.1016\/j.cell.2026.06.013_bib84","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1038\/s41592-023-01943-7","article-title":"Unsupervised removal of systematic background noise from droplet-based single-cell experiments using CellBender","volume":"20","author":"Fleming","year":"2023","journal-title":"Nat. Methods"},{"key":"10.1016\/j.cell.2026.06.013_bib85","doi-asserted-by":"crossref","DOI":"10.12688\/f1000research.73600.1","article-title":"Doublet identification in single-cell sequencing data using scDblFinder","volume":"10","author":"Germain","year":"2021","journal-title":"F1000Res"},{"key":"10.1016\/j.cell.2026.06.013_bib86","doi-asserted-by":"crossref","DOI":"10.1186\/s13059-021-02547-0","article-title":"DropletQC: improved identification of empty droplets and damaged cells in single-cell RNA-seq data","volume":"22","author":"Muskovic","year":"2021","journal-title":"Genome Biol."},{"key":"10.1016\/j.cell.2026.06.013_bib87","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/s41587-023-01767-y","article-title":"Dictionary learning for integrative, multimodal and scalable single-cell analysis","volume":"42","author":"Hao","year":"2024","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.cell.2026.06.013_bib88","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1038\/s41592-019-0619-0","article-title":"Fast, sensitive and accurate integration of single-cell data with Harmony","volume":"16","author":"Korsunsky","year":"2019","journal-title":"Nat. Methods"},{"key":"10.1016\/j.cell.2026.06.013_bib89","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-019-41695-z","article-title":"From Louvain to Leiden: guaranteeing well-connected communities","volume":"9","author":"Traag","year":"2019","journal-title":"Sci. Rep."},{"key":"10.1016\/j.cell.2026.06.013_bib90","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/s41586-021-03465-8","article-title":"Comparative cellular analysis of motor cortex in human, marmoset and mouse","volume":"598","author":"Bakken","year":"2021","journal-title":"Nature"},{"key":"10.1016\/j.cell.2026.06.013_bib91","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2023.113622","article-title":"ATM-deficiency-induced microglial activation promotes neurodegeneration in ataxia-telangiectasia","volume":"43","author":"Lai","year":"2024","journal-title":"Cell Rep."},{"key":"10.1016\/j.cell.2026.06.013_bib92","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1111\/1755-0998.13128","article-title":"Dirichlet-multinomial modelling outperforms alternatives for analysis of microbiome and other ecological count data","volume":"20","author":"Harrison","year":"2020","journal-title":"Mol. Ecol. Resour."},{"key":"10.1016\/j.cell.2026.06.013_bib93","doi-asserted-by":"crossref","DOI":"10.1038\/s42003-021-02146-6","article-title":"NEBULA is a fast negative binomial mixed model for differential or co-expression analysis of large-scale multi-subject single-cell data","volume":"4","author":"He","year":"2021","journal-title":"Commun. Biol."},{"key":"10.1016\/j.cell.2026.06.013_bib94","doi-asserted-by":"crossref","first-page":"2366","DOI":"10.1038\/s41593-024-01774-5","article-title":"Integrated multimodal cell atlas of Alzheimer's disease","volume":"27","author":"Gabitto","year":"2024","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.cell.2026.06.013_bib95","doi-asserted-by":"crossref","DOI":"10.1002\/cpcb.51","article-title":"Transcription Factor-Mediated Differentiation of Human iPSCs into Neurons","volume":"79","author":"Fernandopulle","year":"2018","journal-title":"Curr. Protoc. Cell Biol."}],"container-title":["Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0092867426007002?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0092867426007002?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T15:03:23Z","timestamp":1788447803000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0092867426007002"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":95,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["S0092867426007002"],"URL":"https:\/\/doi.org\/10.1016\/j.cell.2026.06.013","relation":{},"ISSN":["0092-8674"],"issn-type":[{"value":"0092-8674","type":"print"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Recurrent patterns of TOP1-mediated neuronal genomic damage shared by major neurodegenerative disorders","name":"articletitle","label":"Article Title"},{"value":"Cell","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.cell.2026.06.013","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Author(s). Published by Elsevier Inc.","name":"copyright","label":"Copyright"}]}}