{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:07:11Z","timestamp":1787238431209,"version":"build-2736575974"},"reference-count":93,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2022,2,25]],"date-time":"2022-02-25T00:00:00Z","timestamp":1645747200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Royal Society Sir Henry Dale Fellowship","award":["107643\/B\/15\/Z"],"award-info":[{"award-number":["107643\/B\/15\/Z"]}]},{"name":"Wellcome-Beit Prize","award":["107643\/B\/15\/A"],"award-info":[{"award-number":["107643\/B\/15\/A"]}]},{"DOI":"10.13039\/501100000288","name":"Royal Society","doi-asserted-by":"publisher","award":["RGS\/R1\/201043"],"award-info":[{"award-number":["RGS\/R1\/201043"]}],"id":[{"id":"10.13039\/501100000288","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004815","name":"Isaac Newton Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004815","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Wellcome Trust ISSF"},{"name":"University of Cambridge Joint Research Grants Scheme"},{"name":"AstraZeneca PhD studentship"},{"name":"CRUK Cambridge Centre"},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["T32GM007753"],"award-info":[{"award-number":["T32GM007753"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R00 AG054748"],"award-info":[{"award-number":["R00 AG054748"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["DP2 AG072437"],"award-info":[{"award-number":["DP2 AG072437"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Charles H. Hood Child Health Foundation"},{"name":"Suh Kyungbae Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,3,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The autosomal recessive genome instability disorder Ataxia\u2013telangiectasia, caused by mutations in ATM kinase, is characterized by the progressive loss of cerebellar neurons. We find that DNA damage associated with ATM loss results in dysfunctional behaviour of human microglia, immune cells of the central nervous system. Microglial dysfunction is mediated by the pro-inflammatory RELB\/p52 non-canonical NF-\u03baB transcriptional pathway and leads to excessive phagocytic clearance of neuronal material. Activation of the RELB\/p52 pathway in ATM-deficient microglia is driven by persistent DNA damage and is dependent on the NIK kinase. Activation of non-canonical NF-\u03baB signalling is also observed in cerebellar microglia of individuals with Ataxia\u2013telangiectasia. These results provide insights into the underlying mechanisms of aberrant microglial behaviour in ATM deficiency, potentially contributing to neurodegeneration in Ataxia\u2013telangiectasia.<\/jats:p>","DOI":"10.1093\/nar\/gkac104","type":"journal-article","created":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T15:12:25Z","timestamp":1643901145000},"page":"2700-2718","source":"Crossref","is-referenced-by-count":36,"title":["Persistent DNA damage associated with ATM kinase deficiency promotes microglial dysfunction"],"prefix":"10.1093","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3382-225X","authenticated-orcid":false,"given":"Julie","family":"Bourseguin","sequence":"first","affiliation":[{"name":"Department of Biochemistry, University of Cambridge, 80 Tennis Court road, CambridgeCB2 1GA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Cambridge, 80 Tennis Court road, CambridgeCB2 1GA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5951-8862","authenticated-orcid":false,"given":"Emily","family":"Talbot","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Cambridge, 80 Tennis Court road, CambridgeCB2 1GA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9822-0834","authenticated-orcid":false,"given":"Liana","family":"Hardy","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Cambridge, 80 Tennis Court road, CambridgeCB2 1GA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4720-9229","authenticated-orcid":false,"given":"Jenny","family":"Lai","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomics, Boston Children's Hospital; Department of Pediatrics, Harvard Medical School, Boston, MA\u00a002215, USA"},{"name":"Broad Institute of MIT and Harvard, Cambridge, MA\u00a002142, USA"},{"name":"Program in Neuroscience, Harvard University, Boston, MA\u00a002115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6233-4215","authenticated-orcid":false,"given":"Ailsa\u00a0M","family":"Jeffries","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cell, and Cancer Biology, University of Massachusetts Medical School, Worcester, MA\u00a001605, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4175-1073","authenticated-orcid":false,"given":"Michael A","family":"Lodato","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cell, and Cancer Biology, University of Massachusetts Medical School, Worcester, MA\u00a001605, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6574-9261","authenticated-orcid":false,"given":"Eunjung Alice","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomics, Boston Children's Hospital; Department of Pediatrics, Harvard Medical School, Boston, MA\u00a002215, USA"},{"name":"Broad Institute of MIT and Harvard, Cambridge, MA\u00a002142, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7439-9320","authenticated-orcid":false,"given":"Svetlana\u00a0V","family":"Khoronenkova","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Cambridge, 80 Tennis Court road, CambridgeCB2 1GA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,2,25]]},"reference":[{"key":"2022032100043818100_B1","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1126\/science.7792600","article-title":"A single ataxia telangiectasia gene with a product similar to PI-3 kinase","volume":"268","author":"Savitsky","year":"1995","journal-title":"Science"},{"key":"2022032100043818100_B2","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.molcel.2008.05.017","article-title":"ATM signaling facilitates repair of DNA double-strand breaks associated with heterochromatin","volume":"31","author":"Goodarzi","year":"2008","journal-title":"Mol. Cell"},{"key":"2022032100043818100_B3","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/s41467-018-07729-2","article-title":"ATM orchestrates the DNA-damage response to counter toxic non-homologous end-joining at broken replication forks","volume":"10","author":"Balmus","year":"2019","journal-title":"Nat. Commun."},{"key":"2022032100043818100_B4","doi-asserted-by":"crossref","first-page":"102950","DOI":"10.1016\/j.dnarep.2020.102950","article-title":"The cerebellar degeneration in ataxia-telangiectasia: A case for genome instability","volume":"95","author":"Shiloh","year":"2020","journal-title":"DNA Repair (Amst)"},{"key":"2022032100043818100_B5","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1186\/s13023-016-0543-7","article-title":"Ataxia telangiectasia: a review","volume":"11","author":"Rothblum-Oviatt","year":"2016","journal-title":"Orphanet. J. Rare. Dis."},{"key":"2022032100043818100_B6","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1038\/s41593-018-0242-x","article-title":"Microglia in neurodegeneration","volume":"21","author":"Hickman","year":"2018","journal-title":"Nat. Neurosci."},{"key":"2022032100043818100_B7","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1038\/nature23672","article-title":"A somatic mutation in erythro-myeloid progenitors causes neurodegenerative disease","volume":"549","author":"Mass","year":"2017","journal-title":"Nature"},{"key":"2022032100043818100_B8","doi-asserted-by":"crossref","first-page":"2147","DOI":"10.1016\/j.neurobiolaging.2014.03.025","article-title":"Priming of microglia in a DNA-repair deficient model of accelerated aging","volume":"35","author":"Raj","year":"2014","journal-title":"Neurobiol. of Aging"},{"key":"2022032100043818100_B9","doi-asserted-by":"crossref","first-page":"e0151026","DOI":"10.1371\/journal.pone.0151026","article-title":"Frataxin Deficiency Promotes Excess Microglial DNA Damage and Inflammation that Is Rescued by PJ34","volume":"11","author":"Shen","year":"2016","journal-title":"PLoS One"},{"key":"2022032100043818100_B10","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1189\/jlb.4VMA0716-316R","article-title":"Rats with a missense mutation in Atm display neuroinflammation and neurodegeneration subsequent to accumulation of cytosolic DNA following unrepaired DNA damage","volume":"101","author":"Quek","year":"2017","journal-title":"J. Leukoc. Biol."},{"key":"2022032100043818100_B11","first-page":"109","article-title":"A rat model of ataxia-telangiectasia: evidence for a neurodegenerative phenotype","volume":"26","author":"Quek","year":"2017","journal-title":"Human molecular genetics"},{"key":"2022032100043818100_B12","doi-asserted-by":"crossref","first-page":"6378","DOI":"10.1523\/JNEUROSCI.0774-19.2019","article-title":"Accumulation of Cytoplasmic DNA Due to ATM Deficiency Activates the Microglial Viral Response System with Neurotoxic Consequences","volume":"39","author":"Song","year":"2019","journal-title":"J Neurosci"},{"key":"2022032100043818100_B13","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1002\/glia.24122","article-title":"Dysfunction of cerebellar microglia in Ataxia-telangiectasia","volume":"70","author":"Levi","year":"2022","journal-title":"Glia"},{"key":"2022032100043818100_B14","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.immuni.2015.01.012","article-title":"DNA Damage Primes the Type I Interferon System via the Cytosolic DNA Sensor STING to Promote Anti-Microbial Innate Immunity","volume":"42","author":"H\u00e4rtlova","year":"2015","journal-title":"Immunity"},{"key":"2022032100043818100_B15","doi-asserted-by":"crossref","first-page":"3940","DOI":"10.1158\/0008-5472.CAN-19-0761","article-title":"Inhibition of ATM Increases Interferon Signaling and Sensitizes Pancreatic Cancer to Immune Checkpoint Blockade Therapy","volume":"79","author":"Zhang","year":"2019","journal-title":"Cancer Res"},{"key":"2022032100043818100_B16","doi-asserted-by":"crossref","first-page":"e139333","DOI":"10.1172\/JCI139333","article-title":"ATM inhibition enhances cancer immunotherapy by promoting mtDNA leakage and cGAS\/STING activation","volume":"131","author":"Hu","year":"2021","journal-title":"J Clin Invest"},{"key":"2022032100043818100_B17","doi-asserted-by":"crossref","first-page":"e13468","DOI":"10.1111\/acel.13468","article-title":"Inhibition of the cGAS-STING pathway ameliorates the premature senescence hallmarks of Ataxia-Telangiectasia brain organoids","volume":"20","author":"Aguado","year":"2021","journal-title":"Aging Cell"},{"key":"2022032100043818100_B18","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":"2022032100043818100_B19","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.tins.2013.12.001","article-title":"The human side of microglia","volume":"37","author":"Smith","year":"2014","journal-title":"Trends Neurosci"},{"key":"2022032100043818100_B20","doi-asserted-by":"crossref","first-page":"12698","DOI":"10.1073\/pnas.0914257107","article-title":"Divergence of human and mouse brain transcriptome highlights Alzheimer disease pathways","volume":"107","author":"Miller","year":"2010","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2022032100043818100_B21","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1038\/s41586-019-1506-7","article-title":"Conserved cell types with divergent features in human versus mouse cortex","volume":"573","author":"Hodge","year":"2019","journal-title":"Nature"},{"key":"2022032100043818100_B22","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/0304-3940(94)11792-H","article-title":"Establishment of human microglial cell lines after transfection of primary cultures of embryonic microglial cells with the SV40 large T antigen","volume":"195","author":"Janabi","year":"1995","journal-title":"Neurosci Lett"},{"key":"2022032100043818100_B23","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s13365-016-0499-3","article-title":"Immortalization of primary microglia: a new platform to study HIV regulation in the central nervous system","volume":"23","author":"Garcia-Mesa","year":"2017","journal-title":"Journal of NeuroVirology"},{"key":"2022032100043818100_B24","doi-asserted-by":"crossref","first-page":"38884","DOI":"10.1074\/jbc.M205518200","article-title":"Effect of mutant alpha-synuclein on dopamine homeostasis in a new human mesencephalic cell line","volume":"277","author":"Lotharius","year":"2002","journal-title":"J Biol Chem"},{"key":"2022032100043818100_B25","doi-asserted-by":"crossref","first-page":"2281","DOI":"10.1038\/nprot.2013.143","article-title":"Genome engineering using the CRISPR-Cas9 system","volume":"8","author":"Ran","year":"2013","journal-title":"Nature Protocols"},{"key":"2022032100043818100_B26","doi-asserted-by":"crossref","first-page":"24356","DOI":"10.1038\/srep24356","article-title":"CRISPR-Cas9D10A nickase-based genotypic and phenotypic screening to enhance genome editing","volume":"6","author":"Chiang","year":"2016","journal-title":"Scientific Reports"},{"key":"2022032100043818100_B27","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.1126\/science.281.5383.1677","article-title":"Activation of the ATM kinase by ionizing radiation and phosphorylation of p53","volume":"281","author":"Canman","year":"1998","journal-title":"Science"},{"key":"2022032100043818100_B28","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1038\/nmeth.4156","article-title":"One-step generation of conditional and reversible gene knockouts","volume":"14","author":"Andersson-Rolf","year":"2017","journal-title":"Nat Methods"},{"key":"2022032100043818100_B29","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1016\/j.dnarep.2008.03.017","article-title":"Poly(ADP-ribose) polymerase-1 modulates DNA repair capacity and prevents formation of DNA double strand breaks","volume":"7","author":"Woodhouse","year":"2008","journal-title":"DNA Repair (Amst)"},{"key":"2022032100043818100_B30","doi-asserted-by":"crossref","first-page":"3997","DOI":"10.1073\/pnas.1416031112","article-title":"ATM prevents DSB formation by coordinating SSB repair and cell cycle progression","volume":"112","author":"Khoronenkova","year":"2015","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2022032100043818100_B31","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/S1383-5718(02)00251-6","article-title":"A cross-platform public domain PC image-analysis program for the comet assay","volume":"534","author":"Konca","year":"2003","journal-title":"Mutat. Res."},{"key":"2022032100043818100_B32","doi-asserted-by":"crossref","first-page":"R100","DOI":"10.1186\/gb-2006-7-10-r100","article-title":"CellProfiler: image analysis software for identifying and quantifying cell phenotypes","volume":"7","author":"Carpenter","year":"2006","journal-title":"Genome Biol."},{"key":"2022032100043818100_B33","doi-asserted-by":"crossref","DOI":"10.1101\/2021.09.09.459619","article-title":"Single-nucleus transcriptomic analyses reveal microglial activation underlying cerebellar degeneration in Ataxia Telangiectasia","author":"Lai","year":"2021"},{"key":"2022032100043818100_B34","doi-asserted-by":"crossref","first-page":"17023","DOI":"10.1038\/sigtrans.2017.23","article-title":"NF-\u03baB signaling in inflammation","volume":"2","author":"Liu","year":"2017","journal-title":"Signal Transduct. Target. Ther."},{"key":"2022032100043818100_B35","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1038\/nri.2017.52","article-title":"The non-canonical NF-\u03baB pathway in immunity and inflammation","volume":"17","author":"Sun","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"2022032100043818100_B36","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1038\/nature25432","article-title":"Chromosomal instability drives metastasis through a cytosolic DNA response","volume":"553","author":"Bakhoum","year":"2018","journal-title":"Nature"},{"key":"2022032100043818100_B37","doi-asserted-by":"crossref","first-page":"13544","DOI":"10.1073\/pnas.0506577102","article-title":"Discovering statistically significant pathways in expression profiling studies","volume":"102","author":"Tian","year":"2005","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2022032100043818100_B38","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1186\/s12974-018-1288-0","article-title":"The human microglial HMC3 cell line: Where do we stand? A systematic literature review","volume":"15","author":"Dello\u00a0Russo","year":"2018","journal-title":"J. of Neuroinflammation"},{"key":"2022032100043818100_B39","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1093\/hmg\/5.4.433","article-title":"Predominance of null mutations in ataxia-telangiectasia","volume":"5","author":"Gilad","year":"1996","journal-title":"Hum. Mol. Genet."},{"key":"2022032100043818100_B40","doi-asserted-by":"crossref","first-page":"15201","DOI":"10.1074\/jbc.M110.101808","article-title":"Transcription-dependent activation of ataxia telangiectasia mutated prevents DNA-dependent protein kinase-mediated cell death in response to topoisomerase I poison","volume":"285","author":"Sakasai","year":"2010","journal-title":"J. Biol. Chem."},{"key":"2022032100043818100_B41","doi-asserted-by":"crossref","first-page":"1893","DOI":"10.1126\/science.282.5395.1893","article-title":"Linkage of ATM to cell cycle regulation by the Chk2 protein kinase","volume":"282","author":"Matsuoka","year":"1998","journal-title":"Science"},{"key":"2022032100043818100_B42","doi-asserted-by":"crossref","first-page":"11594","DOI":"10.1158\/0008-5472.CAN-06-4138","article-title":"KAP1, a novel substrate for PIKK family members, colocalizes with numerous damage response factors at DNA lesions","volume":"66","author":"White","year":"2006","journal-title":"Cancer Res."},{"key":"2022032100043818100_B43","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1038\/ncb1446","article-title":"Chromatin relaxation in response to DNA double-strand breaks is modulated by a novel ATM- and KAP-1 dependent pathway","volume":"8","author":"Ziv","year":"2006","journal-title":"Nat. Cell. Biol."},{"key":"2022032100043818100_B44","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.molcel.2009.04.025","article-title":"Essential role for DNA-PKcs in DNA double-strand break repair and apoptosis in ATM-deficient lymphocytes","volume":"34","author":"Callen","year":"2009","journal-title":"Mol. Cell."},{"key":"2022032100043818100_B45","first-page":"163","article-title":"CD40\/CD40L dyad in the inflammatory and immune responses in the central nervous system","volume":"3","author":"Chen","year":"2006","journal-title":"Cell Mol. Immunol."},{"key":"2022032100043818100_B46","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1111\/j.1365-2990.2010.01156.x","article-title":"Microglial alterations in human Alzheimer's disease following Abeta42 immunization","volume":"37","author":"Zotova","year":"2011","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"2022032100043818100_B47","doi-asserted-by":"crossref","first-page":"eaat1719","DOI":"10.1126\/sciadv.aat1719","article-title":"The brain-penetrant clinical ATM inhibitor AZD1390 radiosensitizes and improves survival of preclinical brain tumor models","volume":"4","author":"Durant","year":"2018","journal-title":"Sci. Adv."},{"key":"2022032100043818100_B48","doi-asserted-by":"crossref","first-page":"45","DOI":"10.20517\/2394-4722.2017.03","article-title":"DNA damage-induced nuclear factor-kappa B activation and its roles in cancer progression","volume":"3","author":"Wang","year":"2017","journal-title":"J. Cancer Metastasis Treat."},{"key":"2022032100043818100_B49","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1016\/j.neuron.2014.01.013","article-title":"Microglia induce motor neuron death via the classical NF-kappaB pathway in amyotrophic lateral sclerosis","volume":"81","author":"Frakes","year":"2014","journal-title":"Neuron"},{"key":"2022032100043818100_B50","doi-asserted-by":"crossref","first-page":"6717","DOI":"10.1038\/sj.onc.1209937","article-title":"Post-translational modifications regulating the activity and function of the nuclear factor kappa B pathway","volume":"25","author":"Perkins","year":"2006","journal-title":"Oncogene"},{"key":"2022032100043818100_B51","doi-asserted-by":"crossref","first-page":"646043","DOI":"10.3389\/fimmu.2021.646043","article-title":"Systems-Level Proteomics Evaluation of Microglia Response to Tumor-Supportive Anti-inflammatory Cytokines","volume":"12","author":"Ahuja","year":"2021","journal-title":"Front Immunol."},{"key":"2022032100043818100_B52","doi-asserted-by":"crossref","first-page":"22","DOI":"10.3390\/cells5020022","article-title":"Post-Translational Modifications of RelB NF-kappaB Subunit and Associated Functions","volume":"5","author":"Baud","year":"2016","journal-title":"Cells"},{"key":"2022032100043818100_B53","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/978-94-024-0921-5_4","article-title":"Regulation of IL-6 in Immunity and Diseases","volume":"941","author":"Tanaka","year":"2016","journal-title":"Adv. Exp. Med. Biol."},{"key":"2022032100043818100_B54","doi-asserted-by":"crossref","first-page":"5352","DOI":"10.4049\/jimmunol.164.10.5352","article-title":"Regulation of RANTES chemokine gene expression requires cooperativity between NF-kappa B and IFN-regulatory factor transcription factors","volume":"164","author":"Genin","year":"2000","journal-title":"J. Immunol."},{"key":"2022032100043818100_B55","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1016\/j.cell.2007.07.009","article-title":"NF-kappaB is a negative regulator of IL-1beta secretion as revealed by genetic and pharmacological inhibition of IKKbeta","volume":"130","author":"Greten","year":"2007","journal-title":"Cell"},{"key":"2022032100043818100_B56","doi-asserted-by":"crossref","first-page":"3803","DOI":"10.1073\/pnas.86.10.3803","article-title":"Potential antiinflammatory effects of interleukin 4: suppression of human monocyte tumor necrosis factor alpha, interleukin 1, and prostaglandin E2","volume":"86","author":"Hart","year":"1989","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2022032100043818100_B57","first-page":"1849","article-title":"Increased oxidative stress in ataxia telangiectasia evidenced by alterations in redox state of brains from Atm-deficient mice","volume":"61","author":"Kamsler","year":"2001","journal-title":"Can. Res."},{"key":"2022032100043818100_B58","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/nrm3376","article-title":"New insights into the molecular and cellular functions of poly(ADP-ribose) and PARPs","volume":"13","author":"Gibson","year":"2012","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2022032100043818100_B59","first-page":"179","article-title":"The comet assay. An overview of techniques","volume":"203","author":"Olive","year":"2002","journal-title":"Methods Mol. Biol."},{"key":"2022032100043818100_B60","doi-asserted-by":"crossref","first-page":"13560","DOI":"10.1016\/S0021-9258(18)90729-5","article-title":"Nonintercalative antitumor drugs interfere with the breakage-reunion reaction of mammalian DNA topoisomerase II","volume":"259","author":"Chen","year":"1984","journal-title":"J. Biol. Chem."},{"key":"2022032100043818100_B61","first-page":"391","article-title":"A simple assay of the superoxide generation rate with Tiron as an EPR-visible radical scavenger","volume":"13","author":"Ledenev","year":"1986","journal-title":"Biochem. Int."},{"key":"2022032100043818100_B62","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1016\/j.cell.2018.05.003","article-title":"Disease-Associated Microglia: A Universal Immune Sensor of Neurodegeneration","volume":"173","author":"Deczkowska","year":"2018","journal-title":"Cell"},{"key":"2022032100043818100_B63","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1038\/s41593-019-0566-1","article-title":"Lipid-droplet-accumulating microglia represent a dysfunctional and proinflammatory state in the aging brain","volume":"23","author":"Marschallinger","year":"2020","journal-title":"Nat. Neurosci."},{"key":"2022032100043818100_B64","doi-asserted-by":"crossref","first-page":"3566","DOI":"10.1111\/febs.14323","article-title":"Neurophagy, the phagocytosis of live neurons and synapses by glia, contributes to brain development and disease","volume":"285","author":"Vilalta","year":"2018","journal-title":"FEBS J."},{"key":"2022032100043818100_B65","doi-asserted-by":"crossref","first-page":"5960","DOI":"10.3390\/ijms21175960","article-title":"Microglial Phagocytosis-Rational but Challenging Therapeutic Target in Multiple Sclerosis","volume":"21","author":"Pinto","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"2022032100043818100_B66","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1111\/j.1471-4159.2011.07255.x","article-title":"Rapid, complete and large-scale generation of post-mitotic neurons from the human LUHMES cell line","volume":"119","author":"Scholz","year":"2011","journal-title":"J. Neurochem."},{"key":"2022032100043818100_B67","doi-asserted-by":"crossref","first-page":"108882","DOI":"10.1016\/j.celrep.2021.108882","article-title":"Microglial identity and inflammatory responses are controlled by the combined effects of neurons and astrocytes","volume":"34","author":"Baxter","year":"2021","journal-title":"Cell Rep."},{"key":"2022032100043818100_B68","doi-asserted-by":"crossref","first-page":"2030","DOI":"10.1038\/s41467-021-22301-1","article-title":"Loss of microglial SIRPalpha promotes synaptic pruning in preclinical models of neurodegeneration","volume":"12","author":"Ding","year":"2021","journal-title":"Nat. Commun."},{"key":"2022032100043818100_B69","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1016\/S1097-2765(04)00131-5","article-title":"Active repression of antiapoptotic gene expression by Rela(p65) NF-kappa B","volume":"13","author":"Campbell","year":"2004","journal-title":"Mol. Cell."},{"key":"2022032100043818100_B70","doi-asserted-by":"crossref","first-page":"4273","DOI":"10.1158\/0008-5472.CAN-04-3494","article-title":"Nuclear factor-kappaB induced by doxorubicin is deficient in phosphorylation and acetylation and represses nuclear factor-kappaB-dependent transcription in cancer cells","volume":"65","author":"Ho","year":"2005","journal-title":"Cancer Res."},{"key":"2022032100043818100_B71","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1038\/ncb2463","article-title":"Fbxw7alpha- and GSK3-mediated degradation of p100 is a pro-survival mechanism in multiple myeloma","volume":"14","author":"Busino","year":"2012","journal-title":"Nat. Cell. Biol."},{"key":"2022032100043818100_B72","doi-asserted-by":"crossref","first-page":"4820","DOI":"10.1038\/ncomms5820","article-title":"Negative regulation of NF-kappaB activity by brain-specific TRIpartite Motif protein 9","volume":"5","author":"Shi","year":"2014","journal-title":"Nat. Commun."},{"key":"2022032100043818100_B73","doi-asserted-by":"crossref","first-page":"8416","DOI":"10.1093\/nar\/gku529","article-title":"ATM regulates NF-kappaB-dependent immediate-early genes via RelA Ser 276 phosphorylation coupled to CDK9 promoter recruitment","volume":"42","author":"Fang","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"2022032100043818100_B74","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1038\/s41580-020-0244-x","article-title":"Molecular mechanisms and cellular functions of cGAS-STING signalling","volume":"21","author":"Hopfner","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2022032100043818100_B75","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1111\/j.1440-1789.2011.01210.x","article-title":"Heterotopic Purkinje cells in ataxia-telangiectasia","volume":"32","author":"Bottini","year":"2012","journal-title":"Neuropathol."},{"key":"2022032100043818100_B76","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1038\/sj.cdd.4401843","article-title":"Signals from within: the DNA-damage-induced NF-kappaB response","volume":"13","author":"Janssens","year":"2006","journal-title":"Cell Death Differ."},{"key":"2022032100043818100_B77","doi-asserted-by":"crossref","first-page":"4242","DOI":"10.1093\/nar\/24.21.4242","article-title":"Topoisomerase poisons activate the transcription factor NF-kappaB in ACH-2 and CEM cells","volume":"24","author":"Piret","year":"1996","journal-title":"Nucleic Acids Res."},{"key":"2022032100043818100_B78","doi-asserted-by":"crossref","first-page":"9501","DOI":"10.1074\/jbc.275.13.9501","article-title":"NF-kappaB activation by camptothecin. A linkage between nuclear DNA damage and cytoplasmic signaling events","volume":"275","author":"Huang","year":"2000","journal-title":"J. Biol. Chem."},{"key":"2022032100043818100_B79","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/j.molcel.2018.07.034","article-title":"Non-canonical Activation of the DNA Sensing Adaptor STING by ATM and IFI16 Mediates NF-\u03baB Signaling after Nuclear DNA Damage","volume":"71","author":"Dunphy","year":"2018","journal-title":"Mol. Cell"},{"key":"2022032100043818100_B80","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.molcel.2009.09.032","article-title":"A nuclear poly(ADP-ribose)-dependent signalosome confers DNA damage-induced IkappaB kinase activation","volume":"36","author":"Stilmann","year":"2009","journal-title":"Mol. Cell"},{"key":"2022032100043818100_B81","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1042\/bst0290688","article-title":"UV stimulation induces nuclear factor kappaB (NF-kappaB) DNA-binding activity but not transcriptional activation","volume":"29","author":"Campbell","year":"2001","journal-title":"Biochem. Soc. Trans."},{"key":"2022032100043818100_B82","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.immuni.2014.02.006","article-title":"Noncanonical NF-\u03baB pathway controls the production of type I interferons in antiviral innate immunity","volume":"40","author":"Jin","year":"2014","journal-title":"Immunity"},{"key":"2022032100043818100_B83","doi-asserted-by":"crossref","first-page":"104043","DOI":"10.1016\/j.cellimm.2020.104043","article-title":"RelB suppresses type I Interferon signaling in dendritic cells","volume":"349","author":"Saha","year":"2020","journal-title":"Cell Immunol."},{"key":"2022032100043818100_B84","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/S0006-2952(01)00709-2","article-title":"S phase dependence and involvement of NF-kappaB activating kinase to NF-kappaB activation by camptothecin","volume":"62","author":"Habraken","year":"2001","journal-title":"Biochem Pharmacol."},{"key":"2022032100043818100_B85","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1016\/S1097-2765(03)00227-2","article-title":"Modulation of NF-kappaB activity by exchange of dimers","volume":"11","author":"Saccani","year":"2003","journal-title":"Mol. Cell."},{"key":"2022032100043818100_B86","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1038\/nn.4222","article-title":"Microglial brain region-dependent diversity and selective regional sensitivities to aging","volume":"19","author":"Grabert","year":"2016","journal-title":"Nat. Neurosci."},{"key":"2022032100043818100_B87","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1016\/j.cell.2016.04.001","article-title":"Progranulin Deficiency Promotes Circuit-Specific Synaptic Pruning by Microglia via Complement Activation","volume":"165","author":"Lui","year":"2016","journal-title":"Cell"},{"key":"2022032100043818100_B88","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1126\/science.aad8373","article-title":"Complement and microglia mediate early synapse loss in Alzheimer mouse models","volume":"352","author":"Hong","year":"2016","journal-title":"Science"},{"key":"2022032100043818100_B89","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1038\/s41593-020-00780-7","article-title":"Phagocyte-mediated synapse removal in cortical neuroinflammation is promoted by local calcium accumulation","volume":"24","author":"Jafari","year":"2021","journal-title":"Nat. Neurosci."},{"key":"2022032100043818100_B90","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.dnarep.2018.10.001","article-title":"Inactive Atm abrogates DSB repair in mouse cerebellum more than does Atm loss, without causing a neurological phenotype","volume":"72","author":"Tal","year":"2018","journal-title":"DNA Repair (Amst)"},{"key":"2022032100043818100_B91","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1002\/dneu.22572","article-title":"Cerebellar microglia are dynamically unique and survey Purkinje neurons in vivo","volume":"78","author":"Stowell","year":"2018","journal-title":"Dev. Neurobiol."},{"key":"2022032100043818100_B92","doi-asserted-by":"crossref","first-page":"14722","DOI":"10.1038\/s41598-019-51246-1","article-title":"Increased interactions and engulfment of dendrites by microglia precede Purkinje cell degeneration in a mouse model of Niemann Pick Type-C","volume":"9","author":"Kavetsky","year":"2019","journal-title":"Sci. Rep."},{"key":"2022032100043818100_B93","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1038\/s41593-018-0192-3","article-title":"Epigenetic regulation of brain region-specific microglia clearance activity","volume":"21","author":"Ayata","year":"2018","journal-title":"Nat. Neurosci."}],"container-title":["Nucleic Acids Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/nar\/article-pdf\/50\/5\/2700\/42920095\/gkac104.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/nar\/article-pdf\/50\/5\/2700\/42920095\/gkac104.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,20]],"date-time":"2022-03-20T20:06:09Z","timestamp":1647806769000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/nar\/article\/50\/5\/2700\/6536895"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,25]]},"references-count":93,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,2,25]]},"published-print":{"date-parts":[[2022,3,21]]}},"URL":"https:\/\/doi.org\/10.1093\/nar\/gkac104","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.06.02.446712","asserted-by":"object"}]},"ISSN":["0305-1048","1362-4962"],"issn-type":[{"value":"0305-1048","type":"print"},{"value":"1362-4962","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,3,21]]},"published":{"date-parts":[[2022,2,25]]}}}