{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:23:17Z","timestamp":1791397397067,"version":"4.3.3"},"reference-count":82,"publisher":"Springer Science and Business Media LLC","issue":"8074","license":[{"start":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T00:00:00Z","timestamp":1750809600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T00:00:00Z","timestamp":1750809600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nature"],"published-print":{"date-parts":[[2025,7,31]]},"DOI":"10.1038\/s41586-025-09210-9","type":"journal-article","created":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T11:02:44Z","timestamp":1750849364000},"page":"1400-1409","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Mechanism of cytarabine-induced neurotoxicity"],"prefix":"10.1038","volume":"643","author":[{"given":"Jia-Cheng","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8272-1228","authenticated-orcid":false,"given":"Dongpeng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elsa","family":"Callen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5279-9035","authenticated-orcid":false,"given":"Chuanyuan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5166-9858","authenticated-orcid":false,"given":"Santiago","family":"Noriega","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yafang","family":"Shang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2904-1378","authenticated-orcid":false,"given":"David","family":"Sch\u00fcrmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yawei","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7506-2711","authenticated-orcid":false,"given":"Gokul N.","family":"Ramadoss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2216-313X","authenticated-orcid":false,"given":"Raj","family":"Chari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Wong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4466-2391","authenticated-orcid":false,"given":"Yongge","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1455-3963","authenticated-orcid":false,"given":"Yuan","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5686-9969","authenticated-orcid":false,"given":"Peter D.","family":"Aplan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5296-8051","authenticated-orcid":false,"given":"Michael E.","family":"Ward","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8874-8704","authenticated-orcid":false,"given":"Nathaniel","family":"Heintz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1870-1775","authenticated-orcid":false,"given":"Anjana","family":"Rao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0485-3778","authenticated-orcid":false,"given":"Peter J.","family":"McKinnon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4255-9016","authenticated-orcid":false,"given":"Keith W.","family":"Caldecott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1843-6147","authenticated-orcid":false,"given":"Primo","family":"Sch\u00e4r","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0333-6872","authenticated-orcid":false,"given":"Fei-Long","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferenc","family":"Livak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5164-2765","authenticated-orcid":false,"given":"Wei","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8952-7268","authenticated-orcid":false,"given":"Andr\u00e9","family":"Nussenzweig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,25]]},"reference":[{"key":"9210_CR1","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1126\/science.1169786","volume":"324","author":"S Kriaucionis","year":"2009","unstructured":"Kriaucionis, S. & Heintz, N. The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain. Science 324, 929\u2013930 (2009).","journal-title":"Science"},{"key":"9210_CR2","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1038\/nrclinonc.2015.152","volume":"13","author":"JB Stone","year":"2016","unstructured":"Stone, J. B. & DeAngelis, L. M. Cancer-treatment-induced neurotoxicity\u2014focus on newer treatments. Nat. Rev. Clin. Oncol. 13, 92\u2013105 (2016).","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"9210_CR3","doi-asserted-by":"publisher","first-page":"78","DOI":"10.3389\/fmolb.2017.00078","volume":"4","author":"AJ Berdis","year":"2017","unstructured":"Berdis, A. J. Inhibiting DNA polymerases as a therapeutic intervention against cancer. Front. Mol. Biosci. 4, 78 (2017).","journal-title":"Front. Mol. Biosci."},{"key":"9210_CR4","first-page":"4050","volume":"42","author":"RJ Fram","year":"1982","unstructured":"Fram, R. J. & Kufe, D. W. DNA strand breaks caused by inhibitors of DNA synthesis: 1-\u03b2-d-arabinofuranosylcytosine and aphidicolin. Cancer Res. 42, 4050\u20134053 (1982).","journal-title":"Cancer Res."},{"key":"9210_CR5","first-page":"6110","volume":"51","author":"P Huang","year":"1991","unstructured":"Huang, P., Chubb, S., Hertel, L. W., Grindey, G. B. & Plunkett, W. Action of 2\u2032,2\u2032-difluorodeoxycytidine on DNA synthesis. Cancer Res. 51, 6110\u20136117 (1991).","journal-title":"Cancer Res."},{"key":"9210_CR6","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1038\/nrc1074","volume":"3","author":"DB Longley","year":"2003","unstructured":"Longley, D. B., Harkin, D. P. & Johnston, P. G. 5-Fluorouracil: mechanisms of action and clinical strategies. Nat. Rev. Cancer 3, 330\u2013338 (2003).","journal-title":"Nat. Rev. Cancer"},{"key":"9210_CR7","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1016\/S0026-895X(25)09518-5","volume":"38","author":"V Heinemann","year":"1990","unstructured":"Heinemann, V. et al. Inhibition of ribonucleotide reduction in CCRF-CEM cells by 2\u2032,2\u2032-difluorodeoxycytidine. Mol. Pharmacol. 38, 567\u2013572 (1990).","journal-title":"Mol. Pharmacol."},{"key":"9210_CR8","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.cell.2018.10.049","volume":"176","author":"EM Gibson","year":"2019","unstructured":"Gibson, E. M. et al. Methotrexate chemotherapy induces persistent tri-glial dysregulation that underlies chemotherapy-related cognitive impairment. Cell 176, 43\u201355 (2019).","journal-title":"Cell"},{"key":"9210_CR9","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1016\/j.bbr.2019.01.007","volume":"362","author":"DP Jarmolowicz","year":"2019","unstructured":"Jarmolowicz, D. P. et al. 5-Fluorouracil impairs attention and dopamine release in rats. Behav. Brain Res. 362, 319\u2013322 (2019).","journal-title":"Behav. Brain Res."},{"key":"9210_CR10","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1200\/JCO.1987.5.6.927","volume":"5","author":"RH Herzig","year":"1987","unstructured":"Herzig, R. H. et al. Cerebellar toxicity with high-dose cytosine arabinoside. J. Clin. Oncol. 5, 927\u2013932 (1987).","journal-title":"J. Clin. Oncol."},{"key":"9210_CR11","first-page":"1014","volume":"14","author":"DJ Vaughn","year":"1993","unstructured":"Vaughn, D. J., Jarvik, J. G., Hackney, D., Peters, S. & Stadtmauer, E. A. High-dose cytarabine neurotoxicity: MR findings during the acute phase. Am. J. Neuroradiol. 14, 1014\u20131016 (1993).","journal-title":"Am. J. Neuroradiol."},{"key":"9210_CR12","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.blre.2014.09.012","volume":"29","author":"RS Magge","year":"2015","unstructured":"Magge, R. S. & DeAngelis, L. M. The double-edged sword: neurotoxicity of chemotherapy. Blood Rev. 29, 93\u2013100 (2015).","journal-title":"Blood Rev."},{"key":"9210_CR13","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1126\/science.add9838","volume":"378","author":"D Wang","year":"2022","unstructured":"Wang, D. et al. Active DNA demethylation promotes cell fate specification and the DNA damage response. Science 378, 983\u2013989 (2022).","journal-title":"Science"},{"key":"9210_CR14","doi-asserted-by":"publisher","first-page":"5653","DOI":"10.1016\/j.cell.2021.10.002","volume":"184","author":"JA Hussmann","year":"2021","unstructured":"Hussmann, J. A. et al. Mapping the genetic landscape of DNA double-strand break repair. Cell 184, 5653\u20135669 (2021).","journal-title":"Cell"},{"key":"9210_CR15","doi-asserted-by":"publisher","DOI":"10.1002\/cpcb.51","volume":"79","author":"MS Fernandopulle","year":"2018","unstructured":"Fernandopulle, M. S. et al. Transcription factor-mediated differentiation of human iPSCs into neurons. Curr. Protoc. Cell Biol. 79, e51 (2018).","journal-title":"Curr. Protoc. Cell Biol."},{"key":"9210_CR16","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1038\/s41596-018-0113-7","volume":"14","author":"B Wang","year":"2019","unstructured":"Wang, B. et al. Integrative analysis of pooled CRISPR genetic screens using MAGeCKFlute. Nat. Protoc. 14, 756\u2013780 (2019).","journal-title":"Nat. Protoc."},{"key":"9210_CR17","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-33742-7","volume":"13","author":"RO Georges","year":"2022","unstructured":"Georges, R. O. et al. Acute deletion of TET enzymes results in aneuploidy in mouse embryonic stem cells through decreased expression of Khdc3. Nat. Commun. 13, 6230 (2022).","journal-title":"Nat. Commun."},{"key":"9210_CR18","doi-asserted-by":"publisher","first-page":"1774","DOI":"10.1016\/j.cell.2016.11.009","volume":"167","author":"S Ladstatter","year":"2016","unstructured":"Ladstatter, S. & Tachibana-Konwalski, K. A surveillance mechanism ensures repair of DNA lesions during zygotic reprogramming. Cell 167, 1774\u20131787 (2016).","journal-title":"Cell"},{"key":"9210_CR19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/0304-3940(95)12247-8","volume":"203","author":"Y Enokido","year":"1996","unstructured":"Enokido, Y., Araki, T., Aizawa, S. & Hatanaka, H. p53 involves cytosine arabinoside-induced apoptosis in cultured cerebellar granule neurons. Neurosci. Lett. 203, 1\u20134 (1996).","journal-title":"Neurosci. Lett."},{"key":"9210_CR20","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1038\/s41589-018-0021-8","volume":"14","author":"B Nabet","year":"2018","unstructured":"Nabet, B. et al. The dTAG system for immediate and target-specific protein degradation. Nat. Chem. Biol. 14, 431\u2013441 (2018).","journal-title":"Nat. Chem. Biol."},{"key":"9210_CR21","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1016\/j.neuron.2018.10.013","volume":"100","author":"EL Yap","year":"2018","unstructured":"Yap, E. L. & Greenberg, M. E. Activity-regulated transcription: bridging the gap between neural activity and behavior. Neuron 100, 330\u2013348 (2018).","journal-title":"Neuron"},{"key":"9210_CR22","doi-asserted-by":"publisher","first-page":"4404","DOI":"10.1016\/j.cell.2023.08.038","volume":"186","author":"V Dileep","year":"2023","unstructured":"Dileep, V. et al. Neuronal DNA double-strand breaks lead to genome structural variations and 3D genome disruption in neurodegeneration. Cell 186, 4404\u20134421 (2023).","journal-title":"Cell"},{"key":"9210_CR23","doi-asserted-by":"publisher","first-page":"1592","DOI":"10.1016\/j.cell.2015.05.032","volume":"161","author":"R Madabhushi","year":"2015","unstructured":"Madabhushi, R. et al. Activity-induced DNA breaks govern the expression of neuronal early-response genes. Cell 161, 1592\u20131605 (2015).","journal-title":"Cell"},{"key":"9210_CR24","doi-asserted-by":"publisher","first-page":"4263","DOI":"10.1038\/s41388-021-01856-9","volume":"40","author":"DA Ramsden","year":"2021","unstructured":"Ramsden, D. A. & Nussenzweig, A. Mechanisms driving chromosomal translocations: lost in time and space. Oncogene 40, 4263\u20134270 (2021).","journal-title":"Oncogene"},{"key":"9210_CR25","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1038\/nprot.2016.043","volume":"11","author":"J Hu","year":"2016","unstructured":"Hu, J. et al. Detecting DNA double-stranded breaks in mammalian genomes by linear amplification-mediated high-throughput genome-wide translocation sequencing. Nat. Protoc. 11, 853\u2013871 (2016).","journal-title":"Nat. Protoc."},{"key":"9210_CR26","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1016\/j.molcel.2016.06.034","volume":"63","author":"A Canela","year":"2016","unstructured":"Canela, A. et al. DNA breaks and end resection measured genome-wide by end sequencing. Mol. Cell 63, 898\u2013911 (2016).","journal-title":"Mol. Cell"},{"key":"9210_CR27","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1038\/s41586-021-03468-5","volume":"593","author":"W Wu","year":"2021","unstructured":"Wu, W. et al. Neuronal enhancers are hotspots for DNA single-strand break repair. Nature 593, 440\u2013444 (2021).","journal-title":"Nature"},{"key":"9210_CR28","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1038\/nature14157","volume":"518","author":"PA Mateos-Gomez","year":"2015","unstructured":"Mateos-Gomez, P. A. et al. Mammalian polymerase \u03b8 promotes alternative NHEJ and suppresses recombination. Nature 518, 254\u2013257 (2015).","journal-title":"Nature"},{"key":"9210_CR29","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1038\/nature14184","volume":"518","author":"R Ceccaldi","year":"2015","unstructured":"Ceccaldi, R. et al. Homologous-recombination-deficient tumours are dependent on Pol\u03b8-mediated repair. Nature 518, 258\u2013262 (2015).","journal-title":"Nature"},{"key":"9210_CR30","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":"9210_CR31","doi-asserted-by":"publisher","DOI":"10.1126\/science.abg2538","volume":"372","author":"LM Morton","year":"2021","unstructured":"Morton, L. M. et al. Radiation-related genomic profile of papillary thyroid carcinoma after the Chernobyl accident. Science 372, eabg2538 (2021).","journal-title":"Science"},{"key":"9210_CR32","doi-asserted-by":"publisher","first-page":"1027","DOI":"10.1056\/NEJMoa1010222","volume":"364","author":"B Lowenberg","year":"2011","unstructured":"Lowenberg, B. et al. Cytarabine dose for acute myeloid leukemia. N. Engl. J. Med. 364, 1027\u20131036 (2011).","journal-title":"N. Engl. J. Med."},{"key":"9210_CR33","doi-asserted-by":"publisher","first-page":"bav028","DOI":"10.1093\/database\/bav028","volume":"2015","author":"J Pinero","year":"2015","unstructured":"Pinero, J. et al. DisGeNET: a discovery platform for the dynamical exploration of human diseases and their genes. Database 2015, bav028 (2015).","journal-title":"Database"},{"key":"9210_CR34","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1016\/j.neuron.2023.10.039","volume":"112","author":"L Tejwani","year":"2024","unstructured":"Tejwani, L. et al. Longitudinal single-cell transcriptional dynamics throughout neurodegeneration in SCA1. Neuron 112, 362\u2013383 (2024).","journal-title":"Neuron"},{"key":"9210_CR35","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1038\/s41594-022-00883-8","volume":"30","author":"Y Tan","year":"2023","unstructured":"Tan, Y. et al. Signal-induced enhancer activation requires Ku70 to read topoisomerase1\u2013DNA covalent complexes. Nat. Struct. Mol. Biol. 30, 148\u2013158 (2023).","journal-title":"Nat. Struct. Mol. Biol."},{"key":"9210_CR36","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abg6363","volume":"7","author":"YD Kwak","year":"2021","unstructured":"Kwak, Y. D. et al. Chromatin architecture at susceptible gene loci in cerebellar Purkinje cells characterizes DNA damage-induced neurodegeneration. Sci. Adv. 7, eabg6363 (2021).","journal-title":"Sci. Adv."},{"key":"9210_CR37","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.66973","volume":"10","author":"E Stoyanova","year":"2021","unstructured":"Stoyanova, E., Riad, M., Rao, A. & Heintz, N. 5-Hydroxymethylcytosine-mediated active demethylation is required for mammalian neuronal differentiation and function. eLife 10, e66973 (2021).","journal-title":"eLife"},{"key":"9210_CR38","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-021-02384-1","volume":"22","author":"A Onodera","year":"2021","unstructured":"Onodera, A. et al. Roles of TET and TDG in DNA demethylation in proliferating and non-proliferating immune cells. Genome Biol. 22, 186 (2021).","journal-title":"Genome Biol."},{"key":"9210_CR39","doi-asserted-by":"publisher","first-page":"1492","DOI":"10.1177\/1078155219898747","volume":"26","author":"H Rahmani","year":"2020","unstructured":"Rahmani, H., Radmehr, M., Hadjibabaie, M. & Solduzian, M. Acute cerebellar toxicity induced by high dose of cytarabine (HiDAC): a case report. J. Oncol. Pharm. Pract. 26, 1492\u20131494 (2020).","journal-title":"J. Oncol. Pharm. Pract."},{"key":"9210_CR40","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10806","volume":"7","author":"AR Weber","year":"2016","unstructured":"Weber, A. R. et al. Biochemical reconstitution of TET1\u2013TDG\u2013BER-dependent active DNA demethylation reveals a highly coordinated mechanism. Nat. Commun. 7, 10806 (2016).","journal-title":"Nat. Commun."},{"key":"9210_CR41","doi-asserted-by":"publisher","first-page":"4833","DOI":"10.1021\/bi100200c","volume":"49","author":"AS Prakasha Gowda","year":"2010","unstructured":"Prakasha Gowda, A. S., Polizzi, J. M., Eckert, K. A. & Spratt, T. E. Incorporation of gemcitabine and cytarabine into DNA by DNA polymerase \u03b2 and ligase III\/XRCC1. Biochemistry 49, 4833\u20134840 (2010).","journal-title":"Biochemistry"},{"key":"9210_CR42","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09917-0","volume":"10","author":"CD Drenberg","year":"2019","unstructured":"Drenberg, C. D. et al. A high-throughput screen indicates gemcitabine and JAK inhibitors may be useful for treating pediatric AML. Nat. Commun. 10, 2189 (2019).","journal-title":"Nat. Commun."},{"key":"9210_CR43","doi-asserted-by":"publisher","first-page":"1564","DOI":"10.1038\/s41588-022-01180-2","volume":"54","author":"LJ Luquette","year":"2022","unstructured":"Luquette, L. J. et al. Single-cell genome sequencing of human neurons identifies somatic point mutation and indel enrichment in regulatory elements. Nat. Genet. 54, 1564\u20131571 (2022).","journal-title":"Nat. Genet."},{"key":"9210_CR44","doi-asserted-by":"crossref","unstructured":"Ganz, J. et al. Contrasting somatic mutation patterns in aging human neurons and oligodendrocytes. Cell 187, 1955\u20131970 (2024).","DOI":"10.1016\/j.cell.2024.02.025"},{"key":"9210_CR45","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2020.102950","volume":"95","author":"Y Shiloh","year":"2020","unstructured":"Shiloh, Y. The cerebellar degeneration in ataxia-telangiectasia: a case for genome instability. DNA Repair 95, 102950 (2020).","journal-title":"DNA Repair"},{"key":"9210_CR46","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-33642-w","volume":"13","author":"J Kim","year":"2022","unstructured":"Kim, J. et al. Prevalence and mechanisms of somatic deletions in single human neurons during normal aging and in DNA repair disorders. Nat. Commun. 13, 5918 (2022).","journal-title":"Nat. Commun."},{"key":"9210_CR47","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1016\/j.tcb.2022.04.010","volume":"32","author":"KW Caldecott","year":"2022","unstructured":"Caldecott, K. W. DNA single-strand break repair and human genetic disease. Trends Cell Biol. 32, 733\u2013745 (2022).","journal-title":"Trends Cell Biol."},{"key":"9210_CR48","doi-asserted-by":"publisher","first-page":"4438","DOI":"10.1016\/j.cell.2023.08.005","volume":"186","author":"V Gazestani","year":"2023","unstructured":"Gazestani, V. et al. Early Alzheimer\u2019s disease pathology in human cortex involves transient cell states. Cell 186, 4438\u20134453 (2023).","journal-title":"Cell"},{"key":"9210_CR49","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.1038\/nn.2900","volume":"14","author":"JU Guo","year":"2011","unstructured":"Guo, J. U. et al. Neuronal activity modifies the DNA methylation landscape in the adult brain. Nat. Neurosci. 14, 1345\u20131351 (2011).","journal-title":"Nat. Neurosci."},{"key":"9210_CR50","doi-asserted-by":"publisher","first-page":"836","DOI":"10.1038\/nn.4008","volume":"18","author":"H Yu","year":"2015","unstructured":"Yu, H. et al. Tet3 regulates synaptic transmission and homeostatic plasticity via DNA oxidation and repair. Nat. Neurosci. 18, 836\u2013843 (2015).","journal-title":"Nat. Neurosci."},{"key":"9210_CR51","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/j.neuron.2019.07.014","volume":"104","author":"R Tian","year":"2019","unstructured":"Tian, R. et al. CRISPR interference-based platform for multimodal genetic screens in human iPSC-derived neurons. Neuron 104, 239\u2013255 (2019).","journal-title":"Neuron"},{"key":"9210_CR52","doi-asserted-by":"publisher","first-page":"5425","DOI":"10.1523\/JNEUROSCI.16-17-05425.1996","volume":"16","author":"Z Xia","year":"1996","unstructured":"Xia, Z., Dudek, H., Miranti, C. K. & Greenberg, M. E. Calcium influx via the NMDA receptor induces immediate early gene transcription by a MAP kinase\/ERK-dependent mechanism. J. Neurosci. 16, 5425\u20135436 (1996).","journal-title":"J. Neurosci."},{"key":"9210_CR53","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0554-4","volume":"15","author":"W Li","year":"2014","unstructured":"Li, W. et al. MAGeCK enables robust identification of essential genes from genome-scale CRISPR\/Cas9 knockout screens. Genome Biol. 15, 554 (2014).","journal-title":"Genome Biol."},{"key":"9210_CR54","doi-asserted-by":"publisher","first-page":"2498","DOI":"10.1101\/gr.1239303","volume":"13","author":"P Shannon","year":"2003","unstructured":"Shannon, P. et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 13, 2498\u20132504 (2003).","journal-title":"Genome Res."},{"key":"9210_CR55","doi-asserted-by":"publisher","first-page":"2611","DOI":"10.1016\/j.molcel.2021.03.034","volume":"81","author":"K Shinoda","year":"2021","unstructured":"Shinoda, K. et al. The dystonia gene THAP1 controls DNA double-strand break repair choice. Mol. Cell 81, 2611\u20132624 (2021).","journal-title":"Mol. Cell"},{"key":"9210_CR56","doi-asserted-by":"publisher","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","volume":"30","author":"AM Bolger","year":"2014","unstructured":"Bolger, A. M., Lohse, M. & Usadel, B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30, 2114\u20132120 (2014).","journal-title":"Bioinformatics"},{"key":"9210_CR57","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2009-10-3-r25","volume":"10","author":"B Langmead","year":"2009","unstructured":"Langmead, B., Trapnell, C., Pop, M. & Salzberg, S. L. Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol. 10, R25 (2009).","journal-title":"Genome Biol."},{"key":"9210_CR58","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":"9210_CR59","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":"9210_CR60","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":"9210_CR61","doi-asserted-by":"publisher","first-page":"2204","DOI":"10.1093\/bioinformatics\/btq351","volume":"26","author":"WJ Kent","year":"2010","unstructured":"Kent, W. J., Zweig, A. S., Barber, G., Hinrichs, A. S. & Karolchik, D. BigWig and BigBed: enabling browsing of large distributed datasets. Bioinformatics 26, 2204\u20132207 (2010).","journal-title":"Bioinformatics"},{"key":"9210_CR62","doi-asserted-by":"publisher","first-page":"W160","DOI":"10.1093\/nar\/gkw257","volume":"44","author":"F Ramirez","year":"2016","unstructured":"Ramirez, F. et al. deepTools2: a next generation web server for deep-sequencing data analysis. Nucleic Acids Res. 44, W160\u2013W165 (2016).","journal-title":"Nucleic Acids Res."},{"key":"9210_CR63","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":"9210_CR64","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1186\/1471-2105-10-232","volume":"10","author":"Y Xi","year":"2009","unstructured":"Xi, Y. & Li, W. BSMAP: whole genome bisulfite sequence MAPping program. BMC Bioinformatics 10, 232 (2009).","journal-title":"BMC Bioinformatics"},{"key":"9210_CR65","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":"9210_CR66","doi-asserted-by":"publisher","DOI":"10.1093\/gigascience\/giab008","volume":"10","author":"P Danecek","year":"2021","unstructured":"Danecek, P. et al. Twelve years of SAMtools and BCFtools. Gigascience 10, giab008 (2021).","journal-title":"Gigascience"},{"key":"9210_CR67","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":"9210_CR68","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":"9210_CR69","first-page":"100141","volume":"2","author":"T Wu","year":"2021","unstructured":"Wu, T. et al. clusterProfiler 4.0: a universal enrichment tool for interpreting omics data. Innovation 2, 100141 (2021).","journal-title":"Innovation"},{"key":"9210_CR70","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1093\/bioinformatics\/btu684","volume":"31","author":"G Yu","year":"2015","unstructured":"Yu, G., Wang, L. G., Yan, G. R. & He, Q. Y. DOSE: an R\/Bioconductor package for disease ontology semantic and enrichment analysis. Bioinformatics 31, 608\u2013609 (2015).","journal-title":"Bioinformatics"},{"key":"9210_CR71","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1038\/s41587-019-0114-2","volume":"37","author":"AM Newman","year":"2019","unstructured":"Newman, A. M. et al. Determining cell type abundance and expression from bulk tissues with digital cytometry. Nat. Biotechnol. 37, 773\u2013782 (2019).","journal-title":"Nat. Biotechnol."},{"key":"9210_CR72","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1038\/s41586-023-06812-z","volume":"624","author":"Z Yao","year":"2023","unstructured":"Yao, Z. et al. A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain. Nature 624, 317\u2013332 (2023).","journal-title":"Nature"},{"key":"9210_CR73","doi-asserted-by":"publisher","first-page":"1350","DOI":"10.1016\/j.molcel.2020.01.004","volume":"77","author":"KR Barnett","year":"2020","unstructured":"Barnett, K. R. et al. ATAC-Me captures prolonged DNA methylation of dynamic chromatin accessibility loci during cell fate transitions. Mol. Cell 77, 1350\u20131364 (2020).","journal-title":"Mol. Cell"},{"key":"9210_CR74","doi-asserted-by":"publisher","unstructured":"Li, H. Aligning sequence reads, clone sequences and assembly contigs with BWA-MEM. Preprint at https:\/\/doi.org\/10.48550\/arXiv.1303.3997 (2013).","DOI":"10.48550\/arXiv.1303.3997"},{"key":"9210_CR75","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-019-6041-2","volume":"20","author":"EN Bergstrom","year":"2019","unstructured":"Bergstrom, E. N. et al. SigProfilerMatrixGenerator: a tool for visualizing and exploring patterns of small mutational events. BMC Genomics 20, 685 (2019).","journal-title":"BMC Genomics"},{"key":"9210_CR76","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1038\/s41588-024-01692-z","volume":"56","author":"M Vega-Sendino","year":"2024","unstructured":"Vega-Sendino, M. et al. The homeobox transcription factor DUXBL controls exit from totipotency. Nat. Genet. 56, 697\u2013709 (2024).","journal-title":"Nat. Genet."},{"key":"9210_CR77","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/nmeth.1923","volume":"9","author":"B Langmead","year":"2012","unstructured":"Langmead, B. & Salzberg, S. L. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9, 357\u2013359 (2012).","journal-title":"Nat. Methods"},{"key":"9210_CR78","doi-asserted-by":"publisher","first-page":"26987","DOI":"10.1074\/jbc.M116.751867","volume":"291","author":"M Hammel","year":"2016","unstructured":"Hammel, M. et al. An intrinsically disordered APLF links Ku, DNA-PKcs, and XRCC4-DNA ligase IV in an extended flexible non-homologous end joining complex. J. Biol. Chem. 291, 26987\u201327006 (2016).","journal-title":"J. Biol. Chem."},{"key":"9210_CR79","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1038\/s41587-023-01767-y","volume":"42","author":"Y Hao","year":"2024","unstructured":"Hao, Y. et al. Dictionary learning for integrative, multimodal and scalable single-cell analysis. Nat. Biotechnol. 42, 293\u2013304 (2024).","journal-title":"Nat. Biotechnol."},{"key":"9210_CR80","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1016\/j.cell.2013.04.001","volume":"153","author":"CX Song","year":"2013","unstructured":"Song, C. X. et al. Genome-wide profiling of 5-formylcytosine reveals its roles in epigenetic priming. Cell 153, 678\u2013691 (2013).","journal-title":"Cell"},{"key":"9210_CR81","doi-asserted-by":"publisher","first-page":"e155","DOI":"10.1093\/nar\/gkt599","volume":"41","author":"L Burger","year":"2013","unstructured":"Burger, L., Gaidatzis, D., Schubeler, D. & Stadler, M. B. Identification of active regulatory regions from DNA methylation data. Nucleic Acids Res. 41, e155 (2013).","journal-title":"Nucleic Acids Res."},{"key":"9210_CR82","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1038\/s41588-022-01063-6","volume":"54","author":"T Gu","year":"2022","unstructured":"Gu, T. et al. The disordered N-terminal domain of DNMT3A recognizes H2AK119ub and is required for postnatal development. Nat. Genet. 54, 625\u2013636 (2022).","journal-title":"Nat. Genet."}],"container-title":["Nature"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41586-025-09210-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41586-025-09210-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41586-025-09210-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,6]],"date-time":"2025-09-06T22:23:56Z","timestamp":1757197436000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41586-025-09210-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,25]]},"references-count":82,"journal-issue":{"issue":"8074","published-print":{"date-parts":[[2025,7,31]]}},"alternative-id":["9210"],"URL":"https:\/\/doi.org\/10.1038\/s41586-025-09210-9","relation":{},"ISSN":["0028-0836","1476-4687"],"issn-type":[{"value":"0028-0836","type":"print"},{"value":"1476-4687","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,25]]},"assertion":[{"value":"21 January 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 May 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 June 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}