{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T07:02:57Z","timestamp":1793430177440,"version":"4.5.0"},"reference-count":81,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,10,25]],"date-time":"2019-10-25T00:00:00Z","timestamp":1571961600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,10,25]],"date-time":"2019-10-25T00:00:00Z","timestamp":1571961600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004710","name":"Fondazione Umberto Veronesi","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004710","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"U.S. Department of Health & Human Services | NIH | National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["1UO1 ES011044"],"award-info":[{"award-number":["1UO1 ES011044"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Accumulation of DNA lesions causing transcription stress is associated with natural and accelerated aging and culminates with profound metabolic alterations. Our understanding of the mechanisms governing metabolic redesign upon genomic instability, however, is highly rudimentary. Using <jats:italic>Ercc1<\/jats:italic>-defective mice and <jats:italic>Xpg<\/jats:italic> knock-out mice, we demonstrate that combined defects in transcription-coupled DNA repair (TCR) and in nucleotide excision repair\u00a0(NER) directly affect bioenergetics due to declined transcription, leading to increased ATP levels. This in turn inhibits glycolysis allosterically and favors glucose rerouting through the pentose phosphate shunt, eventually enhancing production of NADPH-reducing equivalents. In NER\/TCR-defective mutants, augmented NADPH is not counterbalanced by increased production of pro-oxidants and thus pentose phosphate potentiation culminates in an over-reduced redox state. Skin fibroblasts from the TCR disease Cockayne syndrome confirm results in animal models. Overall, these findings unravel a mechanism connecting DNA damage and transcriptional stress to metabolic redesign and protective antioxidant defenses.<\/jats:p>","DOI":"10.1038\/s41467-019-12640-5","type":"journal-article","created":{"date-parts":[[2019,10,25]],"date-time":"2019-10-25T18:52:58Z","timestamp":1572029578000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":85,"title":["DNA damage and transcription stress cause ATP-mediated redesign of metabolism and potentiation of anti-oxidant buffering"],"prefix":"10.1038","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8696-2603","authenticated-orcid":false,"given":"Chiara","family":"Milanese","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00edntia R.","family":"Bombardieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Sepe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sander","family":"Barnhoorn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0633-1332","authenticated-orcid":false,"given":"C\u00e9sar","family":"Pay\u00e1n-Gom\u00e9z","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2115-778X","authenticated-orcid":false,"given":"Donatella","family":"Caruso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Audano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Pedretti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilbert P.","family":"Vermeij","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata M. C.","family":"Brandt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akos","family":"Gyenis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirjam M.","family":"Wamelink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annelieke S.","family":"de Wit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roel C.","family":"Janssens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9","family":"Leen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9 B. P.","family":"van Kuilenburg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5000-3619","authenticated-orcid":false,"given":"Nico","family":"Mitro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan H. J.","family":"Hoeijmakers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pier G.","family":"Mastroberardino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,10,25]]},"reference":[{"key":"12640_CR1","doi-asserted-by":"publisher","first-page":"1475","DOI":"10.1056\/NEJMra0804615","volume":"361","author":"JH Hoeijmakers","year":"2009","unstructured":"Hoeijmakers, J. H. DNA damage, aging, and cancer. N. Engl. J. Med. 361, 1475\u20131485 (2009).","journal-title":"N. Engl. J. Med."},{"key":"12640_CR2","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1021\/cr040483f","volume":"106","author":"LC Gillet","year":"2006","unstructured":"Gillet, L. C. & Scharer, O. D. Molecular mechanisms of mammalian global genome nucleotide excision repair. Chem. Rev. 106, 253\u2013276 (2006).","journal-title":"Chem. Rev."},{"key":"12640_CR3","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1038\/nrm3822","volume":"15","author":"JA Marteijn","year":"2014","unstructured":"Marteijn, J. A., Lans, H., Vermeulen, W. & Hoeijmakers, J. H. Understanding nucleotide excision repair and its roles in cancer and ageing. Nat. Rev. Mol. Cell Biol. 15, 465\u2013481 (2014).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"12640_CR4","doi-asserted-by":"publisher","first-page":"1038","DOI":"10.1038\/nature05456","volume":"444","author":"LJ Niedernhofer","year":"2006","unstructured":"Niedernhofer, L. J. et al. A new progeroid syndrome reveals that genotoxic stress suppresses the somatotroph axis. Nature 444, 1038\u20131043 (2006).","journal-title":"Nature"},{"key":"12640_CR5","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1002\/hep.24713","volume":"55","author":"SQ Gregg","year":"2012","unstructured":"Gregg, S. Q. et al. A mouse model of accelerated liver aging caused by a defect in DNA repair. Hepatology 55, 609\u2013621 (2012).","journal-title":"Hepatology"},{"key":"12640_CR6","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1146\/annurev-pharmtox-010814-124316","volume":"56","author":"WP Vermeij","year":"2016","unstructured":"Vermeij, W. P., Hoeijmakers, J. H. & Pothof, J. Genome integrity in aging: human syndromes, mouse models, and therapeutic options. Annu. Rev. Pharm. Toxicol. 56, 427\u2013445 (2016).","journal-title":"Annu. Rev. Pharm. Toxicol."},{"key":"12640_CR7","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1038\/ncb1866","volume":"11","author":"GA Garinis","year":"2009","unstructured":"Garinis, G. A. et al. Persistent transcription-blocking DNA lesions trigger somatic growth attenuation associated with longevity. Nat. Cell Biol. 11, 604\u2013615 (2009).","journal-title":"Nat. Cell Biol."},{"key":"12640_CR8","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.freeradbiomed.2010.03.025","volume":"49","author":"J Cadet","year":"2010","unstructured":"Cadet, J., Douki, T. & Ravanat, J. L. Oxidatively generated base damage to cellular DNA. Free Radic. Biol. Med. 49, 9\u201321 (2010).","journal-title":"Free Radic. Biol. Med."},{"key":"12640_CR9","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1146\/annurev-genet-112414-055257","volume":"49","author":"E Watson","year":"2015","unstructured":"Watson, E., Yilmaz, L. S. & Walhout, A. J. Understanding metabolic regulation at a systems level: metabolite sensing, mathematical predictions, and model organisms. Annu. Rev. Genet. 49, 553\u2013575 (2015).","journal-title":"Annu. Rev. Genet."},{"key":"12640_CR10","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1007\/BF02578899","volume":"39","author":"AH Stouthamer","year":"1973","unstructured":"Stouthamer, A. H. A theoretical study on the amount of ATP required for synthesis of microbial cell material. Antonie Van. Leeuwenhoek 39, 545\u2013565 (1973).","journal-title":"Antonie Van. Leeuwenhoek"},{"key":"12640_CR11","doi-asserted-by":"publisher","first-page":"2586","DOI":"10.1016\/j.jmb.2015.06.021","volume":"427","author":"MH Pontes","year":"2015","unstructured":"Pontes, M. H., Sevostyanova, A. & Groisman, E. A. When Too Much ATP Is Bad for Protein Synthesis. J. Mol. Biol. 427, 2586\u20132594 (2015).","journal-title":"J. Mol. Biol."},{"key":"12640_CR12","doi-asserted-by":"publisher","first-page":"15779","DOI":"10.1073\/pnas.0808480105","volume":"105","author":"CY Jao","year":"2008","unstructured":"Jao, C. Y. & Salic, A. Exploring RNA transcription and turnover in vivo by using click chemistry. Proc. Natl Acad. Sci. USA 105, 15779\u201315784 (2008).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"12640_CR13","doi-asserted-by":"publisher","first-page":"958","DOI":"10.1002\/hep.1840380422","volume":"38","author":"MD Chipchase","year":"2003","unstructured":"Chipchase, M. D., O\u2019Neill, M. & Melton, D. W. Characterization of premature liver polyploidy in DNA repair (Ercc1)-deficient mice. Hepatology 38, 958\u2013966 (2003).","journal-title":"Hepatology"},{"issue":"9","key":"12640_CR14","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1096\/fasebj.14.9.1073","volume":"14","author":"FATIMA N\u00da\u00d1EZ","year":"2000","unstructured":"Nunez F., Chipchase M. D., Clarke A. R., Melton D. W. Nucleotide excision repair gene (ERCC1) deficiency causes G(2) arrest in hepatocytes and a reduction in liver binucleation: the role of p53 and p21. FASEB J. 14, 1073\u20131082 (2000).","journal-title":"The FASEB Journal"},{"key":"12640_CR15","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1016\/S0960-9822(06)00190-4","volume":"7","author":"G Weeda","year":"1997","unstructured":"Weeda, G. et al. Disruption of mouse ERCC1 results in a novel repair syndrome with growth failure, nuclear abnormalities and senescence. Curr. Biol. 7, 427\u2013439 (1997).","journal-title":"Curr. Biol."},{"key":"12640_CR16","doi-asserted-by":"publisher","first-page":"E6770","DOI":"10.1073\/pnas.1716581115","volume":"115","author":"L Daniel","year":"2018","unstructured":"Daniel, L. et al. Mechanistic insights in transcription-coupled nucleotide excision repair of ribosomal DNA. Proc. Natl Acad. Sci. USA 115, E6770\u2013E6779 (2018).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"12640_CR17","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1038\/nature19329","volume":"537","author":"WP Vermeij","year":"2016","unstructured":"Vermeij, W. P. et al. Restricted diet delays accelerated ageing and genomic stress in DNA-repair-deficient mice. Nature 537, 427\u2013431 (2016).","journal-title":"Nature"},{"key":"12640_CR18","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1146\/annurev.ge.12.120178.001553","volume":"12","author":"W Sauerbier","year":"1978","unstructured":"Sauerbier, W. & Hercules, K. Gene and transcription unit mapping by radiation effects. Annu. Rev. Genet. 12, 329\u2013363 (1978).","journal-title":"Annu. Rev. Genet."},{"key":"12640_CR19","doi-asserted-by":"publisher","first-page":"6582","DOI":"10.1073\/pnas.0308181101","volume":"101","author":"BC McKay","year":"2004","unstructured":"McKay, B. C. et al. Regulation of ultraviolet light-induced gene expression by gene size. Proc. Natl Acad. Sci. USA 101, 6582\u20136586 (2004).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"12640_CR20","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1016\/j.tig.2008.03.008","volume":"24","author":"S Egloff","year":"2008","unstructured":"Egloff, S. & Murphy, S. Cracking the RNA polymerase II CTD code. Trends Genet. 24, 280\u2013288 (2008).","journal-title":"Trends Genet."},{"key":"12640_CR21","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1038\/nrm2921","volume":"11","author":"HD Ulrich","year":"2010","unstructured":"Ulrich, H. D. & Walden, H. Ubiquitin signalling in DNA replication and repair. Nat. Rev. Mol. Cell Biol. 11, 479 (2010).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"12640_CR22","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1016\/j.cell.2005.04.010","volume":"121","author":"BP Somesh","year":"2005","unstructured":"Somesh, B. P. et al. Multiple mechanisms confining RNA polymerase II ubiquitylation to polymerases undergoing transcriptional arrest. Cell 121, 913\u2013923 (2005).","journal-title":"Cell"},{"key":"12640_CR23","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/S0921-8777(00)00064-1","volume":"485","author":"BC McKay","year":"2001","unstructured":"McKay, B. C. et al. UV light-induced degradation of RNA polymerase II is dependent on the Cockayne\u2019s syndrome A and B proteins but not p53 or MLH1. Mutat. Res. 485, 93\u2013105 (2001).","journal-title":"Mutat. Res."},{"key":"12640_CR24","first-page":"423","volume":"1826","author":"P Icard","year":"2012","unstructured":"Icard, P. & Lincet, H. A global view of the biochemical pathways involved in the regulation of the metabolism of cancer cells. Biochim. Biophys. Acta 1826, 423\u2013433 (2012).","journal-title":"Biochim. Biophys. Acta"},{"key":"12640_CR25","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1016\/j.bbapap.2009.02.006","volume":"1794","author":"MM Marinho-Carvalho","year":"2009","unstructured":"Marinho-Carvalho, M. M., Costa-Mattos, P. V., Spitz, G. A., Zancan, P. & Sola-Penna, M. Calmodulin upregulates skeletal muscle 6-phosphofructo-1-kinase reversing the inhibitory effects of allosteric modulators. Biochim. Biophys. Acta 1794, 1175\u20131180 (2009).","journal-title":"Biochim. Biophys. Acta"},{"key":"12640_CR26","unstructured":"Nelson D. L., Cox M. M., Lehninger A. L. Lehninger Principles of Biochemistry, 4th edn. W. H. Freeman (2005)."},{"key":"12640_CR27","doi-asserted-by":"crossref","first-page":"15675","DOI":"10.1016\/S0021-9258(18)98460-7","volume":"266","author":"K Tornheim","year":"1991","unstructured":"Tornheim, K., Andres, V. & Schultz, V. Modulation by citrate of glycolytic oscillations in skeletal muscle extracts. J. Biol. Chem. 266, 15675\u201315678 (1991).","journal-title":"J. Biol. Chem."},{"key":"12640_CR28","doi-asserted-by":"publisher","DOI":"10.1186\/jbiol61","volume":"6","author":"M Ralser","year":"2007","unstructured":"Ralser, M. et al. Dynamic rerouting of the carbohydrate flux is key to counteracting oxidative stress. J. Biol. 6, 10 (2007).","journal-title":"J. Biol."},{"key":"12640_CR29","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1089\/ars.2010.3629","volume":"15","author":"MP Horowitz","year":"2011","unstructured":"Horowitz, M. P. et al. Single-cell redox imaging demonstrates a distinctive response of dopaminergic neurons to oxidative insults. Antioxid. Redox Signal. 15, 855\u2013871 (2011).","journal-title":"Antioxid. Redox Signal."},{"key":"12640_CR30","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1016\/j.freeradbiomed.2008.06.018","volume":"45","author":"PG Mastroberardino","year":"2008","unstructured":"Mastroberardino, P. G., Orr, A. L., Hu, X., Na, H. M. & Greenamyre, J. T. A FRET-based method to study protein thiol oxidation in histological preparations. Free Radic. Biol. Med 45, 971\u2013981 (2008).","journal-title":"Free Radic. Biol. Med"},{"key":"12640_CR31","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1111\/j.1749-6632.2000.tb06187.x","volume":"899","author":"ER Stadtman","year":"2000","unstructured":"Stadtman, E. R. & Levine, R. L. Protein oxidation. Ann. N. Y Acad. Sci. 899, 191\u2013208 (2000).","journal-title":"Ann. N. Y Acad. Sci."},{"key":"12640_CR32","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1083\/jcb.142.2.365","volume":"142","author":"D Tortorella","year":"1998","unstructured":"Tortorella, D. et al. Dislocation of type I membrane proteins from the ER to the cytosol is sensitive to changes in redox potential. J. Cell Biol. 142, 365\u2013376 (1998).","journal-title":"J. Cell Biol."},{"key":"12640_CR33","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1146\/annurev.bi.40.070171.004115","volume":"40","author":"AW Murray","year":"1971","unstructured":"Murray, A. W. The biological significance of purine salvage. Annu Rev. Biochem. 40, 811\u2013826 (1971).","journal-title":"Annu Rev. Biochem."},{"key":"12640_CR34","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1016\/S1357-4310(99)01459-8","volume":"5","author":"SA Baldwin","year":"1999","unstructured":"Baldwin, S. A., Mackey, J. R., Cass, C. E. & Young, J. D. Nucleoside transporters: molecular biology and implications for therapeutic development. Mol. Med. Today 5, 216\u2013224 (1999).","journal-title":"Mol. Med. Today"},{"key":"12640_CR35","doi-asserted-by":"publisher","first-page":"C1776","DOI":"10.1152\/ajpcell.2001.281.6.C1776","volume":"281","author":"TD Batiuk","year":"2001","unstructured":"Batiuk, T. D., Schnizlein-Bick, C., Plotkin, Z. & Dagher, P. C. Guanine nucleosides and Jurkat cell death: roles of ATP depletion and accumulation of deoxyribonucleotides. Am. J. Physiol. Cell Physiol. 281, C1776\u2013C1784 (2001).","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"12640_CR36","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1016\/j.cell.2011.03.044","volume":"145","author":"AC Bester","year":"2011","unstructured":"Bester, A. C. et al. Nucleotide deficiency promotes genomic instability in early stages of cancer development. Cell 145, 435\u2013446 (2011).","journal-title":"Cell"},{"key":"12640_CR37","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1001\/jamapediatrics.2015.0754","volume":"169","author":"HJ Vernon","year":"2015","unstructured":"Vernon, H. J. Inborn errors of metabolism: advances in diagnosis and therapy. JAMA Pediatr. 169, 778\u2013782 (2015).","journal-title":"JAMA Pediatr."},{"key":"12640_CR38","doi-asserted-by":"publisher","first-page":"e1004686","DOI":"10.1371\/journal.pgen.1004686","volume":"10","author":"S Barnhoorn","year":"2014","unstructured":"Barnhoorn, S. et al. Cell-autonomous progeroid changes in conditional mouse models for repair endonuclease XPG deficiency. PLoS Genet. 10, e1004686 (2014).","journal-title":"PLoS Genet."},{"key":"12640_CR39","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/0027-5107(79)90231-8","volume":"62","author":"W Keijzer","year":"1979","unstructured":"Keijzer, W. et al. A seventh complementation group in excision-deficient xeroderma pigmentosum. Mutat. Res. 62, 183\u2013190 (1979).","journal-title":"Mutat. Res."},{"key":"12640_CR40","first-page":"185","volume":"53","author":"W Vermeulen","year":"1993","unstructured":"Vermeulen, W., Jaeken, J., Jaspers, N. G., Bootsma, D. & Hoeijmakers, J. H. Xeroderma pigmentosum complementation group G associated with Cockayne syndrome. Am. J. Hum. Genet. 53, 185\u2013192 (1993).","journal-title":"Am. J. Hum. Genet."},{"key":"12640_CR41","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1046\/j.0022-202x.2001.01673.x","volume":"118","author":"P Lalle","year":"2002","unstructured":"Lalle, P., Nouspikel, T., Constantinou, A., Thorel, F. & Clarkson, S. G. The founding members of xeroderma pigmentosum group G produce XPG protein with severely impaired endonuclease activity. J. Invest. Dermatol. 118, 344\u2013351 (2002).","journal-title":"J. Invest. Dermatol."},{"key":"12640_CR42","doi-asserted-by":"publisher","first-page":"3116","DOI":"10.1073\/pnas.94.7.3116","volume":"94","author":"T Nouspikel","year":"1997","unstructured":"Nouspikel, T., Lalle, P., Leadon, S. A., Cooper, P. K. & Clarkson, S. G. A common mutational pattern in Cockayne syndrome patients from xeroderma pigmentosum group G: implications for a second XPG function. Proc. Natl Acad. Sci. USA 94, 3116\u20133121 (1997).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"12640_CR43","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1111\/j.1474-9726.2012.00815.x","volume":"11","author":"B Pascucci","year":"2012","unstructured":"Pascucci, B. et al. An altered redox balance mediates the hypersensitivity of Cockayne syndrome primary fibroblasts to oxidative stress. Aging Cell 11, 520\u2013529 (2012).","journal-title":"Aging Cell"},{"key":"12640_CR44","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1016\/j.ajhg.2014.12.012","volume":"96","author":"A Singh","year":"2015","unstructured":"Singh, A., Compe, E., Le May, N. & Egly, J. M. TFIIH subunit alterations causing xeroderma pigmentosum and trichothiodystrophy specifically disturb several steps during transcription. Am. J. Hum. Genet. 96, 194\u2013207 (2015).","journal-title":"Am. J. Hum. Genet."},{"key":"12640_CR45","doi-asserted-by":"publisher","first-page":"2744","DOI":"10.1093\/nar\/gkv148","volume":"43","author":"LC Andrade-Lima","year":"2015","unstructured":"Andrade-Lima, L. C., Veloso, A., Paulsen, M. T., Menck, C. F. & Ljungman, M. DNA repair and recovery of RNA synthesis following exposure to ultraviolet light are delayed in long genes. Nucleic Acids Res. 43, 2744\u20132756 (2015).","journal-title":"Nucleic Acids Res."},{"key":"12640_CR46","doi-asserted-by":"publisher","first-page":"714","DOI":"10.1111\/j.1474-9726.2012.00828.x","volume":"11","author":"J Wang","year":"2012","unstructured":"Wang, J., Clauson, C. L., Robbins, P. D., Niedernhofer, L. J. & Wang, Y. The oxidative DNA lesions 8,5\u2019-cyclopurines accumulate with aging in a tissue-specific manner. Aging Cell 11, 714\u2013716 (2012).","journal-title":"Aging Cell"},{"key":"12640_CR47","doi-asserted-by":"publisher","first-page":"22355","DOI":"10.1074\/jbc.M002259200","volume":"275","author":"PJ Brooks","year":"2000","unstructured":"Brooks, P. J. et al. The oxidative DNA lesion 8,5\u2019-(S)-cyclo-2\u2019-deoxyadenosine is repaired by the nucleotide excision repair pathway and blocks gene expression in mammalian cells. J. Biol. Chem. 275, 22355\u201322362 (2000).","journal-title":"J. Biol. Chem."},{"key":"12640_CR48","doi-asserted-by":"publisher","first-page":"3832","DOI":"10.1073\/pnas.070471597","volume":"97","author":"I Kuraoka","year":"2000","unstructured":"Kuraoka, I. et al. Removal of oxygen free-radical-induced 5\u2019,8-purine cyclodeoxynucleosides from DNA by the nucleotide excision-repair pathway in human cells. Proc. Natl Acad. Sci. USA 97, 3832\u20133837 (2000).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"12640_CR49","doi-asserted-by":"publisher","first-page":"e1000161","DOI":"10.1371\/journal.pgen.1000161","volume":"4","author":"B Schumacher","year":"2008","unstructured":"Schumacher, B. et al. Delayed and accelerated aging share common longevity assurance mechanisms. PLoS Genet. 4, e1000161 (2008).","journal-title":"PLoS Genet."},{"key":"12640_CR50","doi-asserted-by":"publisher","first-page":"e2","DOI":"10.1371\/journal.pbio.0050002","volume":"5","author":"I van der Pluijm","year":"2007","unstructured":"van der Pluijm, I. et al. Impaired genome maintenance suppresses the growth hormone-insulin-like growth factor 1 axis in mice with Cockayne syndrome. PLoS Biol. 5, e2 (2007).","journal-title":"PLoS Biol."},{"key":"12640_CR51","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1128\/JB.00852-08","volume":"191","author":"MC Jewett","year":"2009","unstructured":"Jewett, M. C., Miller, M. L., Chen, Y. & Swartz, J. R. Continued protein synthesis at low [ATP] and [GTP] enables cell adaptation during energy limitation. J. Bacteriol. 191, 1083\u20131091 (2009).","journal-title":"J. Bacteriol."},{"key":"12640_CR52","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/S1097-2765(03)00266-1","volume":"12","author":"HD Murray","year":"2003","unstructured":"Murray, H. D., Schneider, D. A. & Gourse, R. L. Control of rRNA expression by small molecules is dynamic and nonredundant. Mol. Cell 12, 125\u2013134 (2003).","journal-title":"Mol. Cell"},{"key":"12640_CR53","doi-asserted-by":"publisher","first-page":"802","DOI":"10.1016\/j.cell.2016.07.031","volume":"166","author":"C Lopez-Otin","year":"2016","unstructured":"Lopez-Otin, C., Galluzzi, L., Freije, J. M., Madeo, F. & Kroemer, G. Metabolic control of longevity. Cell 166, 802\u2013821 (2016).","journal-title":"Cell"},{"key":"12640_CR54","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1016\/j.cmet.2014.10.008","volume":"20","author":"I Shimizu","year":"2014","unstructured":"Shimizu, I., Yoshida, Y., Suda, M. & Minamino, T. DNA damage response and metabolic disease. Cell Metab. 20, 967\u2013977 (2014).","journal-title":"Cell Metab."},{"key":"12640_CR55","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1016\/j.exger.2010.12.001","volume":"46","author":"DK Ingram","year":"2011","unstructured":"Ingram, D. K. & Roth, G. S. Glycolytic inhibition as a strategy for developing calorie restriction mimetics. Exp. Gerontol. 46, 148\u2013154 (2011).","journal-title":"Exp. Gerontol."},{"key":"12640_CR56","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1111\/brv.12140","volume":"90","author":"A Stincone","year":"2015","unstructured":"Stincone, A. et al. The return of metabolism: biochemistry and physiology of the pentose phosphate pathway. Biol. Rev. Camb. Philos. Soc. 90, 927\u2013963 (2015).","journal-title":"Biol. Rev. Camb. Philos. Soc."},{"issue":"7","key":"12640_CR57","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.1021\/cn400079y","volume":"4","author":"Winnie Jeng","year":"2013","unstructured":"Jeng W., Loniewska M. M., Wells P. G. Brain glucose-6-phosphate dehydrogenase protects against endogenous oxidative DNA damage and neurodegeneration in aged mice. ACS Chem Neurosci. 4, 1123\u20131132 (2013).","journal-title":"ACS Chemical Neuroscience"},{"key":"12640_CR58","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1038\/emboj.2010.330","volume":"30","author":"C Cosentino","year":"2011","unstructured":"Cosentino, C., Grieco, D. & Costanzo, V. ATM activates the pentose phosphate pathway promoting anti-oxidant defence and DNA repair. EMBO J. 30, 546\u2013555 (2011).","journal-title":"EMBO J."},{"key":"12640_CR59","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1002\/emmm.201000096","volume":"2","author":"L Shao","year":"2010","unstructured":"Shao, L., Goronzy, J. J. & Weyand, C. M. DNA-dependent protein kinase catalytic subunit mediates T-cell loss in rheumatoid arthritis. EMBO Mol. Med. 2, 415\u2013427 (2010).","journal-title":"EMBO Mol. Med."},{"key":"12640_CR60","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1016\/j.immuni.2016.09.013","volume":"45","author":"Y Li","year":"2016","unstructured":"Li, Y. et al. Deficient activity of the nuclease MRE11A Induces T cell aging and promotes arthritogenic effector functions in patients with rheumatoid arthritis. Immunity 45, 903\u2013916 (2016).","journal-title":"Immunity"},{"key":"12640_CR61","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1038\/nrrheum.2017.49","volume":"13","author":"CM Weyand","year":"2017","unstructured":"Weyand, C. M. & Goronzy, J. J. Immunometabolism in early and late stages of rheumatoid arthritis. Nat. Rev. Rheumatol. 13, 291\u2013301 (2017).","journal-title":"Nat. Rev. Rheumatol."},{"key":"12640_CR62","first-page":"331ra338","volume":"8","author":"Z Yang","year":"2016","unstructured":"Yang, Z. et al. Restoring oxidant signaling suppresses proarthritogenic T cell effector functions in rheumatoid arthritis. Sci. Transl. Med. 8, 331ra338 (2016).","journal-title":"Sci. Transl. Med."},{"key":"12640_CR63","doi-asserted-by":"publisher","first-page":"3059","DOI":"10.1073\/pnas.0809620106","volume":"106","author":"VI Perez","year":"2009","unstructured":"Perez, V. I. et al. Protein stability and resistance to oxidative stress are determinants of longevity in the longest-living rodent, the naked mole-rat. Proc. Natl Acad. Sci. USA 106, 3059\u20133064 (2009).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"12640_CR64","doi-asserted-by":"publisher","first-page":"1283","DOI":"10.1016\/j.addr.2009.07.015","volume":"61","author":"LP Yap","year":"2009","unstructured":"Yap, L. P., Garcia, J. V., Han, D. & Cadenas, E. The energy-redox axis in aging and age-related neurodegeneration. Adv. Drug Deliv. Rev. 61, 1283\u20131298 (2009).","journal-title":"Adv. Drug Deliv. Rev."},{"key":"12640_CR65","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1007\/s10048-012-0351-8","volume":"14","author":"C Poulton","year":"2013","unstructured":"Poulton, C. et al. Progressive cerebellar atrophy and polyneuropathy: expanding the spectrum of PNKP mutations. Neurogenetics 14, 43\u201351 (2013).","journal-title":"Neurogenetics"},{"key":"12640_CR66","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1016\/j.cell.2007.06.044","volume":"130","author":"NS Rajasekaran","year":"2007","unstructured":"Rajasekaran, N. S. et al. Human alpha B-crystallin mutation causes oxido-reductive stress and protein aggregation cardiomyopathy in mice. Cell 130, 427\u2013439 (2007).","journal-title":"Cell"},{"key":"12640_CR67","doi-asserted-by":"publisher","first-page":"1493","DOI":"10.1016\/j.freeradbiomed.2008.01.002","volume":"44","author":"PI Moreira","year":"2008","unstructured":"Moreira, P. I. et al. Nucleic acid oxidation in Alzheimer disease. Free Radic. Biol. Med. 44, 1493\u20131505 (2008).","journal-title":"Free Radic. Biol. Med."},{"key":"12640_CR68","doi-asserted-by":"publisher","first-page":"1866","DOI":"10.1016\/j.celrep.2016.04.071","volume":"15","author":"S Sepe","year":"2016","unstructured":"Sepe, S. et al. Inefficient DNA Repair is an aging-related modifier of Parkinson\u2019s disease. Cell Rep. 15, 1866\u20131875 (2016).","journal-title":"Cell Rep."},{"issue":"8","key":"12640_CR69","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1016\/j.dnarep.2013.04.009","volume":"12","author":"Sara Sepe","year":"2013","unstructured":"Sepe S., Payan-Gomez C., Milanese C., Hoeijmakers J. H., Mastroberardino P. G. Nucleotide excision repair in chronic neurodegenerative diseases. DNA Repair 12, 568\u2013577 (2013).","journal-title":"DNA Repair"},{"key":"12640_CR70","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1016\/0024-3205(82)90761-5","volume":"31","author":"A Richardson","year":"1982","unstructured":"Richardson, A. & Cheung, H. T. Current concepts: I. The relationship between age-related changes in gene expression, protein turnover, and the responsiveness of an organism to stimuli. Life Sci. 31, 605\u2013613 (1982).","journal-title":"Life Sci."},{"key":"12640_CR71","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/0047-6374(78)90037-4","volume":"8","author":"T Castle","year":"1978","unstructured":"Castle, T., Katz, A. & Richardson, A. Comparison of RNA synthesis by liver nuclei from rats of various ages. Mech. Ageing Dev. 8, 383\u2013395 (1978).","journal-title":"Mech. Ageing Dev."},{"key":"12640_CR72","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1038\/nature04844","volume":"441","author":"R Bahar","year":"2006","unstructured":"Bahar, R. et al. Increased cell-to-cell variation in gene expression in ageing mouse heart. Nature 441, 1011\u20131014 (2006).","journal-title":"Nature"},{"key":"12640_CR73","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/S0091-679X(08)61797-5","volume":"13","author":"PO Seglen","year":"1976","unstructured":"Seglen, P. O. Preparation of isolated rat liver cells. Methods Cell Biol. 13, 29\u201383 (1976).","journal-title":"Methods Cell Biol."},{"key":"12640_CR74","doi-asserted-by":"publisher","first-page":"30444","DOI":"10.1074\/jbc.M112.378091","volume":"287","author":"J Balzarini","year":"2012","unstructured":"Balzarini, J. et al. Introduction of a fluorine atom at C3 of 3-deazauridine shifts its antimetabolic activity from inhibition of CTP synthetase to inhibition of orotidylate decarboxylase, an early event in the de novo pyrimidine nucleotide biosynthesis pathway. J. Biol. Chem. 287, 30444\u201330454 (2012).","journal-title":"J. Biol. Chem."},{"key":"12640_CR75","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1038\/s41419-018-0848-7","volume":"9","author":"C Milanese","year":"2018","unstructured":"Milanese, C. et al. Activation of the DNA damage response in vivo in synucleinopathy models of Parkinson\u2019s disease. Cell Death Dis. 9, 818 (2018).","journal-title":"Cell Death Dis."},{"key":"12640_CR76","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1089\/ars.2017.6992","volume":"28","author":"C Milanese","year":"2018","unstructured":"Milanese, C. et al. Mitochondrial complex I reversible S-nitrosation improves bioenergetics and is protective in Parkinson\u2019s disease. Antioxid. Redox Signal 28, 44\u201361 (2018).","journal-title":"Antioxid. Redox Signal"},{"key":"12640_CR77","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1016\/S0076-6879(94)33040-9","volume":"233","author":"RL Levine","year":"1994","unstructured":"Levine, R. L., Williams, J. A., Stadtman, E. R. & Shacter, E. Carbonyl assays for determination of oxidatively modified proteins. Methods Enzymol. 233, 346\u2013357 (1994).","journal-title":"Methods Enzymol."},{"key":"12640_CR78","doi-asserted-by":"publisher","first-page":"e12333","DOI":"10.1371\/journal.pone.0012333","volume":"5","author":"J Clark","year":"2010","unstructured":"Clark, J. et al. Oral N-acetyl-cysteine attenuates loss of dopaminergic terminals in alpha-synuclein overexpressing mice. PLoS ONE 5, e12333 (2010).","journal-title":"PLoS ONE"},{"key":"12640_CR79","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1007\/s13311-015-0404-4","volume":"13","author":"RC Reyes","year":"2016","unstructured":"Reyes, R. C. et al. Neuronal glutathione content and antioxidant capacity can be normalized in situ by N-acetyl cysteine concentrations attained in human cerebrospinal fluid. Neurotherapeutics 13, 217\u2013225 (2016).","journal-title":"Neurotherapeutics"},{"key":"12640_CR80","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1002\/ana.22162","volume":"69","author":"AE Berman","year":"2011","unstructured":"Berman, A. E. et al. N-acetylcysteine prevents loss of dopaminergic neurons in the EAAC1-\/- mouse. Ann. Neurol. 69, 509\u2013520 (2011).","journal-title":"Ann. Neurol."},{"key":"12640_CR81","doi-asserted-by":"publisher","first-page":"e8762","DOI":"10.1371\/journal.pone.0008762","volume":"5","author":"F Pan-Montojo","year":"2010","unstructured":"Pan-Montojo, F. et al. Progression of Parkinson\u2019s disease pathology is reproduced by intragastric administration of rotenone in mice. PLoS ONE 5, e8762 (2010).","journal-title":"PLoS ONE"}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41467-019-12640-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-019-12640-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-019-12640-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T01:45:58Z","timestamp":1671241558000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41467-019-12640-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,25]]},"references-count":81,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["12640"],"URL":"https:\/\/doi.org\/10.1038\/s41467-019-12640-5","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,25]]},"assertion":[{"value":"21 October 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 September 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 October 2019","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"}}],"article-number":"4887"}}