{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T14:04:19Z","timestamp":1782137059766,"version":"3.54.5"},"reference-count":41,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T00:00:00Z","timestamp":1767916800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000957","name":"Alzheimer&apos;s Association","doi-asserted-by":"publisher","award":["AARG-17\\u2013533363 BK"],"award-info":[{"award-number":["AARG-17\\u2013533363 BK"]}],"id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R21-AG059223"],"award-info":[{"award-number":["R21-AG059223"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01-AG063945"],"award-info":[{"award-number":["R01-AG063945"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["RF1NS112719"],"award-info":[{"award-number":["RF1NS112719"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["PJT168869"],"award-info":[{"award-number":["PJT168869"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI163327"],"award-info":[{"award-number":["R01AI163327"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R56NS073976"],"award-info":[{"award-number":["R56NS073976"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21 AG078635"],"award-info":[{"award-number":["R21 AG078635"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000190","name":"University of Alberta","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000190","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["jbc.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Biological Chemistry"],"published-print":{"date-parts":[[2026,3]]},"DOI":"10.1016\/j.jbc.2026.111156","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T16:18:18Z","timestamp":1768234698000},"page":"111156","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":3,"title":["F2,6BP restores mitochondrial genome integrity in Huntington\u2019s disease"],"prefix":"10.1016","volume":"302","author":[{"given":"Anirban","family":"Chakraborty","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santi M.","family":"Mandal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikita","family":"Mankevich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajam S.","family":"Mani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shandy","family":"Shahabi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manohar","family":"Kodavati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sravan Gopalkrishnashetty","family":"Sreenivasmurthy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nisha","family":"Tapryal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2481-2746","authenticated-orcid":false,"given":"Dale J.","family":"Hamilton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2074-4165","authenticated-orcid":false,"given":"Balaji","family":"Krishnan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muralidhar L.","family":"Hegde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8773-1425","authenticated-orcid":false,"given":"Michael","family":"Weinfeld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gourisankar","family":"Ghosh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4587-687X","authenticated-orcid":false,"given":"Tapas","family":"Hazra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jbc.2026.111156_bib1","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1146\/annurev.neuro.23.1.217","article-title":"Glutamine repeats and neurodegeneration","volume":"23","author":"Zoghbi","year":"2000","journal-title":"Annu. Rev. Neurosci."},{"key":"10.1016\/j.jbc.2026.111156_bib2","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.cell.2015.07.003","article-title":"Identification of genetic factors that modify clinical onset of Huntington's disease","volume":"162","year":"2015","journal-title":"Cell"},{"key":"10.1016\/j.jbc.2026.111156_bib3","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1016\/j.cell.2019.06.036","article-title":"CAG repeat not polyglutamine length determines timing of Huntington's disease onset","volume":"178","year":"2019","journal-title":"Cell"},{"key":"10.1016\/j.jbc.2026.111156_bib4","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.brainresbull.2009.07.010","article-title":"Role of mitochondrial dysfunction in the pathogenesis of Huntington's disease","volume":"80","author":"Quintanilla","year":"2009","journal-title":"Brain Res. Bull."},{"key":"10.1016\/j.jbc.2026.111156_bib5","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.4103\/1673-5374.360289","article-title":"Mitochondria in Huntington's disease: implications in pathogenesis and mitochondrial-targeted therapeutic strategies","volume":"18","author":"Jurcau","year":"2023","journal-title":"Neural. Regen. Res."},{"key":"10.1016\/j.jbc.2026.111156_bib6","doi-asserted-by":"crossref","first-page":"2009","DOI":"10.1093\/brain\/awae007","article-title":"Huntington's disease affects mitochondrial network dynamics predisposing to pathogenic mitochondrial DNA mutations","volume":"147","author":"Neueder","year":"2024","journal-title":"Brain"},{"key":"10.1016\/j.jbc.2026.111156_bib7","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1186\/s40478-024-01802-2","article-title":"Disruption of the mitochondrial network in a mouse model of Huntington's disease visualized by in-tissue multiscale 3D electron microscopy","volume":"12","author":"Martin-Solana","year":"2024","journal-title":"Acta Neuropathol. Commun."},{"key":"10.1016\/j.jbc.2026.111156_bib8","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.mito.2023.03.001","article-title":"A comprehensive perspective of Huntington's disease and mitochondrial dysfunction","volume":"70","author":"Dai","year":"2023","journal-title":"Mitochondrion"},{"key":"10.1016\/j.jbc.2026.111156_bib9","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.freeradbiomed.2013.04.017","article-title":"Role of oxidative DNA damage in mitochondrial dysfunction and huntington's disease pathogenesis","volume":"62","author":"Ayala-Pe\u00f1a","year":"2013","journal-title":"Free Radic. Biol. Med."},{"key":"10.1016\/j.jbc.2026.111156_bib10","doi-asserted-by":"crossref","first-page":"2539","DOI":"10.1093\/nar\/gkp100","article-title":"Oxidative stress induces degradation of mitochondrial DNA","volume":"37","author":"Shokolenko","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.jbc.2026.111156_bib11","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.dnarep.2008.09.004","article-title":"Mitochondrial DNA damage is a hallmark of chemically induced and the R6\/2 transgenic model of Huntington's disease","volume":"8","author":"Acevedo-Torres","year":"2009","journal-title":"DNA Repair (Amst)"},{"key":"10.1016\/j.jbc.2026.111156_bib12","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1016\/j.freeradbiomed.2012.06.008","article-title":"Mitochondrial DNA damage is associated with reduced mitochondrial bioenergetics in Huntington's disease","volume":"53","author":"Siddiqui","year":"2012","journal-title":"Free Radic. Biol. Med."},{"key":"10.1016\/j.jbc.2026.111156_bib13","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1016\/j.neuroscience.2006.08.061","article-title":"DNA repair, mitochondria, and neurodegeneration","volume":"145","author":"Weissman","year":"2007","journal-title":"Neuroscience"},{"key":"10.1016\/j.jbc.2026.111156_bib14","doi-asserted-by":"crossref","first-page":"24176","DOI":"10.1074\/jbc.274.34.24176","article-title":"Molecular cloning of the human gene, PNKP, encoding a polynucleotide kinase 3'-phosphatase and evidence for its role in repair of DNA strand breaks caused by oxidative damage","volume":"274","author":"Jilani","year":"1999","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.jbc.2026.111156_bib15","doi-asserted-by":"crossref","first-page":"24187","DOI":"10.1074\/jbc.274.34.24187","article-title":"Molecular characterization of a human DNA kinase","volume":"274","author":"Karimi-Busheri","year":"1999","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.jbc.2026.111156_bib16","doi-asserted-by":"crossref","first-page":"2465","DOI":"10.15252\/embj.201591363","article-title":"Polynucleotide kinase-phosphatase enables neurogenesis via multiple DNA repair pathways to maintain genome stability","volume":"34","author":"Shimada","year":"2015","journal-title":"EMBO J."},{"key":"10.1016\/j.jbc.2026.111156_bib17","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/ng.526","article-title":"Mutations in PNKP cause microcephaly, seizures and defects in DNA repair","volume":"42","author":"Shen","year":"2010","journal-title":"Nat. Genet."},{"key":"10.1016\/j.jbc.2026.111156_bib18","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/s10048-012-0351-8","article-title":"Progressive cerebellar atrophy and polyneuropathy: expanding the spectrum of PNKP mutations","volume":"14","author":"Poulton","year":"2013","journal-title":"Neurogenetics"},{"key":"10.1016\/j.jbc.2026.111156_bib19","doi-asserted-by":"crossref","DOI":"10.1016\/j.jbc.2023.104714","article-title":"Functional analysis of a conserved site mutation in the DNA end processing enzyme PNKP leading to ataxia with oculomotor apraxia type 4 in humans","volume":"299","author":"Islam","year":"2023","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.jbc.2026.111156_bib20","doi-asserted-by":"crossref","first-page":"5386","DOI":"10.1038\/s41598-022-09097-w","article-title":"Mutations of the DNA repair gene PNKP in a patient with microcephaly, seizures, and developmental delay (MCSZ) presenting with a high-grade brain tumor","volume":"12","author":"Jiang","year":"2022","journal-title":"Sci. Rep."},{"key":"10.1016\/j.jbc.2026.111156_bib21","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.42988","article-title":"Mutant huntingtin impairs PNKP and ATXN3, disrupting DNA repair and transcription","volume":"8","author":"Gao","year":"2019","journal-title":"Elife"},{"key":"10.1016\/j.jbc.2026.111156_bib22","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2406308121","article-title":"Fructose-2,6-bisphosphate restores DNA repair activity of PNKP and ameliorates neurodegenerative symptoms in huntington's disease","volume":"121","author":"Chakraborty","year":"2024","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"10.1016\/j.jbc.2026.111156_bib23","doi-asserted-by":"crossref","first-page":"40544","DOI":"10.1074\/jbc.M508772200","article-title":"Repair of formamidopyrimidines in DNA involves different glycosylases: role of the OGG1, NTH1, and NEIL1 enzymes","volume":"280","author":"Hu","year":"2005","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.jbc.2026.111156_bib24","doi-asserted-by":"crossref","first-page":"2819","DOI":"10.1074\/jbc.M111.272179","article-title":"Role of human DNA glycosylase nei-like 2 (NEIL2) and single strand break repair protein polynucleotide kinase 3'-phosphatase in maintenance of mitochondrial genome","volume":"287","author":"Mandal","year":"2012","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.jbc.2026.111156_bib25","doi-asserted-by":"crossref","first-page":"3484","DOI":"10.1093\/nar\/gkr1245","article-title":"Role of polynucleotide kinase\/phosphatase in mitochondrial DNA repair","volume":"40","author":"Tahbaz","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.jbc.2026.111156_bib26","doi-asserted-by":"crossref","first-page":"8964","DOI":"10.1021\/bi301240y","article-title":"Transcription blockage by bulky end termini at single-strand breaks in the DNA template: differential effects of 5' and 3' adducts","volume":"51","author":"Neil","year":"2012","journal-title":"Biochemistry"},{"key":"10.1016\/j.jbc.2026.111156_bib27","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms13049","article-title":"Classical non-homologous end-joining pathway utilizes nascent RNA for error-free double-strand break repair of transcribed genes","volume":"7","author":"Chakraborty","year":"2016","journal-title":"Nat. Commun."},{"key":"10.1016\/j.jbc.2026.111156_bib28","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.dnarep.2018.05.002","article-title":"Persistent 3'-phosphate termini and increased cytotoxicity of radiomimetic DNA double-strand breaks in cells lacking polynucleotide kinase\/phosphatase despite presence of an alternative 3'-phosphatase","volume":"68","author":"Chalasani","year":"2018","journal-title":"DNA Repair (Amst)"},{"key":"10.1016\/j.jbc.2026.111156_bib29","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.neuron.2007.11.025","article-title":"Suppression of neurodegeneration and increased neurotransmission caused by expanded full-length huntingtin accumulating in the cytoplasm","volume":"57","author":"Romero","year":"2008","journal-title":"Neuron"},{"key":"10.1016\/j.jbc.2026.111156_bib30","doi-asserted-by":"crossref","first-page":"2799","DOI":"10.1093\/hmg\/9.19.2799","article-title":"Dominant phenotypes produced by the HD mutation in STHdh(Q111) striatal cells","volume":"9","author":"Trettel","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.jbc.2026.111156_bib31","doi-asserted-by":"crossref","first-page":"79","DOI":"10.3233\/JHD-160207","article-title":"N-Terminal fragments of huntingtin longer than residue 170 form visible aggregates independently to polyglutamine expansion","volume":"6","author":"Chen","year":"2017","journal-title":"J. Huntingtons Dis."},{"key":"10.1016\/j.jbc.2026.111156_bib32","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1038\/s41582-020-0389-4","article-title":"Huntington disease: new insights into molecular pathogenesis and therapeutic opportunities","volume":"16","author":"Tabrizi","year":"2020","journal-title":"Nat. Rev. Neurol."},{"key":"10.1016\/j.jbc.2026.111156_bib33","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.cmet.2017.06.021","article-title":"Neuronal stimulation triggers neuronal glycolysis and not lactate uptake","volume":"26","author":"Diaz-Garcia","year":"2017","journal-title":"Cell Metab."},{"key":"10.1016\/j.jbc.2026.111156_bib34","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1038\/s12276-024-01211-4","article-title":"Socialized mitochondria: mitonuclear crosstalk in stress","volume":"56","author":"Kim","year":"2024","journal-title":"Exp. Mol. Med."},{"key":"10.1016\/j.jbc.2026.111156_bib35","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.abc9955","article-title":"Mitochondria form contact sites with the nucleus to couple prosurvival retrograde response","volume":"6","author":"Desai","year":"2020","journal-title":"Sci. Adv."},{"key":"10.1016\/j.jbc.2026.111156_bib36","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1016\/j.celrep.2012.10.001","article-title":"Targeting of XJB-5-131 to mitochondria suppresses oxidative DNA damage and motor decline in a mouse model of huntington's disease","volume":"2","author":"Xun","year":"2012","journal-title":"Cell Rep."},{"key":"10.1016\/j.jbc.2026.111156_bib37","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3233\/JHD-210510","article-title":"A double-pronged sword: XJB-5-131 is a suppressor of somatic instability and toxicity in Huntington's disease","volume":"11","author":"Wipf","year":"2022","journal-title":"J. Huntingtons Dis."},{"key":"10.1016\/j.jbc.2026.111156_bib38","first-page":"1524","article-title":"Single nuclei RNA-seq reveals a medium spiny neuron glutamate excitotoxicity signature prior to the onset of neuronal death in an ovine Huntington's disease model","volume":"33","author":"Jiang","year":"2024","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.jbc.2026.111156_bib39","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1038\/s41588-024-01653-6","article-title":"Cell-type-specific CAG repeat expansions and toxicity of mutant huntingtin in human striatum and cerebellum","volume":"56","author":"M\u00e4tlik","year":"2024","journal-title":"Nat. Genet."},{"key":"10.1016\/j.jbc.2026.111156_bib40","doi-asserted-by":"crossref","first-page":"24636","DOI":"10.1074\/jbc.M115.658146","article-title":"Neil2-null mice accumulate oxidized DNA bases in the transcriptionally active sequences of the genome and are susceptible to innate inflammation","volume":"290","author":"Chakraborty","year":"2015","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.jbc.2026.111156_bib41","doi-asserted-by":"crossref","first-page":"2416","DOI":"10.1093\/nar\/gkae002","article-title":"Site-specific acetylation of polynucleotide kinase 3'-phosphatase regulates its distinct role in DNA repair pathways","volume":"52","author":"Islam","year":"2024","journal-title":"Nucleic Acids Res."}],"updated-by":[{"DOI":"10.1016\/j.jbc.2026.113173","type":"erratum","label":"Erratum","source":"publisher","updated":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000}}],"container-title":["Journal of Biological Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0021925826000268?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0021925826000268?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T20:42:05Z","timestamp":1781210525000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0021925826000268"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3]]},"references-count":41,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["S0021925826000268"],"URL":"https:\/\/doi.org\/10.1016\/j.jbc.2026.111156","relation":{},"ISSN":["0021-9258"],"issn-type":[{"value":"0021-9258","type":"print"}],"subject":[],"published":{"date-parts":[[2026,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"F2,6BP restores mitochondrial genome integrity in Huntington\u2019s disease","name":"articletitle","label":"Article Title"},{"value":"Journal of Biological Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jbc.2026.111156","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology.","name":"copyright","label":"Copyright"}],"article-number":"111156"}}