{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T06:05:40Z","timestamp":1792821940200,"version":"4.5.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"14","license":[{"start":{"date-parts":[[2024,6,19]],"date-time":"2024-06-19T00:00:00Z","timestamp":1718755200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,8,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Formaldehyde (FA) is a recognized environmental and metabolic toxin implicated in cancer development and aging. Inherited mutations in the FA-detoxifying enzymes ADH5 and ALDH2 genes lead to FA overload in the severe multisystem AMeD syndrome. FA accumulation causes genome damage including DNA\u2013protein-, inter- and intra-strand crosslinks and oxidative lesions. However, the influence of distinct DNA repair systems on organismal FA resistance remains elusive. We have here investigated the consequence of a range of DNA repair mutants in a model of endogenous FA overload generated by downregulating the orthologs of human ADH5 and ALDH2 in C. elegans. We have focused on the distinct components of nucleotide excision repair (NER) during developmental growth, reproduction and aging. Our results reveal three distinct modes of repair of FA-induced DNA damage: Transcription-coupled repair (TCR) operating NER-independently during developmental growth or through NER during adulthood, and, in concert with global-genome (GG-) NER, in the germline and early embryonic development. Additionally, we show that the Cockayne syndrome B (CSB) factor is involved in the resolution of FA-induced DNA\u2013protein crosslinks, and that the antioxidant and FA quencher N-acetyl-l-cysteine (NAC) reverses the sensitivity of detoxification and DNA repair defects during development, suggesting a therapeutic intervention to revert FA-pathogenic consequences.<\/jats:p>","DOI":"10.1093\/nar\/gkae519","type":"journal-article","created":{"date-parts":[[2024,6,19]],"date-time":"2024-06-19T07:45:56Z","timestamp":1718783156000},"page":"8271-8285","source":"Crossref","is-referenced-by-count":23,"title":["Distinct DNA repair mechanisms prevent formaldehyde toxicity during development, reproduction\u00a0and aging"],"prefix":"10.1093","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1945-9474","authenticated-orcid":false,"given":"Matthias","family":"Rieckher","sequence":"first","affiliation":[{"name":"Institute for Genome Stability in Aging and Disease, Medical Faculty, University and University Hospital of Cologne , Joseph-Stelzmann-Str. 26, 50931\u00a0 Cologne , Germany"},{"name":"Cologne Excellence Cluster for Cellular Stress Responses in Aging-Associated Diseases (CECAD) and Center for Molecular Medicine (CMMC), University of Cologne , Joseph-Stelzmann-Str. 26, 50931\u00a0 Cologne , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Gallrein","sequence":"additional","affiliation":[{"name":"Institute for Genome Stability in Aging and Disease, Medical Faculty, University and University Hospital of Cologne , Joseph-Stelzmann-Str. 26, 50931\u00a0 Cologne , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natividad","family":"Alquezar-Artieda","sequence":"additional","affiliation":[{"name":"Josep Carreras Leukaemia Research Institute (IJC) , Ctra de Can Ruti, Cam\u00ed de les Escoles s\/n, 08916\u00a0 Badalona , Barcelona , Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nour","family":"Bourached-Silva","sequence":"additional","affiliation":[{"name":"Josep Carreras Leukaemia Research Institute (IJC) , Ctra de Can Ruti, Cam\u00ed de les Escoles s\/n, 08916\u00a0 Badalona , Barcelona , Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavana\u00a0Lakshmi","family":"Vaddavalli","sequence":"additional","affiliation":[{"name":"Institute for Genome Stability in Aging and Disease, Medical Faculty, University and University Hospital of Cologne , Joseph-Stelzmann-Str. 26, 50931\u00a0 Cologne , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devin","family":"Mares","sequence":"additional","affiliation":[{"name":"Institute for Genome Stability in Aging and Disease, Medical Faculty, University and University Hospital of Cologne , Joseph-Stelzmann-Str. 26, 50931\u00a0 Cologne , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Backhaus","sequence":"additional","affiliation":[{"name":"Institute for Genome Stability in Aging and Disease, Medical Faculty, University and University Hospital of Cologne , Joseph-Stelzmann-Str. 26, 50931\u00a0 Cologne , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timon","family":"Blindauer","sequence":"additional","affiliation":[{"name":"Institute for Genome Stability in Aging and Disease, Medical Faculty, University and University Hospital of Cologne , Joseph-Stelzmann-Str. 26, 50931\u00a0 Cologne , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ksenia","family":"Greger","sequence":"additional","affiliation":[{"name":"Institute for Genome Stability in Aging and Disease, Medical Faculty, University and University Hospital of Cologne , Joseph-Stelzmann-Str. 26, 50931\u00a0 Cologne , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Wiesner","sequence":"additional","affiliation":[{"name":"Institute for Genome Stability in Aging and Disease, Medical Faculty, University and University Hospital of Cologne , Joseph-Stelzmann-Str. 26, 50931\u00a0 Cologne , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8384-3422","authenticated-orcid":false,"given":"Lucas\u00a0B","family":"Pontel","sequence":"additional","affiliation":[{"name":"Josep Carreras Leukaemia Research Institute (IJC) , Ctra de Can Ruti, Cam\u00ed de les Escoles s\/n, 08916\u00a0 Badalona , Barcelona , Catalonia, Spain"},{"name":"Instituto de Investigaci\u00f3n en Biomedicina de Buenos Aires (IBioBA), CONICET - Partner Institute of the Max Planck Society , C1425FQD, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6097-5238","authenticated-orcid":false,"given":"Bj\u00f6rn","family":"Schumacher","sequence":"additional","affiliation":[{"name":"Institute for Genome Stability in Aging and Disease, Medical Faculty, University and University Hospital of Cologne , Joseph-Stelzmann-Str. 26, 50931\u00a0 Cologne , Germany"},{"name":"Cologne Excellence Cluster for Cellular Stress Responses in Aging-Associated Diseases (CECAD) and Center for Molecular Medicine (CMMC), University of Cologne , Joseph-Stelzmann-Str. 26, 50931\u00a0 Cologne , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,6,19]]},"reference":[{"key":"2024081200022947100_B1","doi-asserted-by":"crossref","first-page":"165","DOI":"10.3390\/cancers14010165","article-title":"The carcinogenic effects of formaldehyde occupational exposure: a systematic review","volume":"14","author":"Protano","year":"2022","journal-title":"Cancers (Basel)"},{"key":"2024081200022947100_B2","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1038\/nature23481","article-title":"Mammals divert endogenous genotoxic formaldehyde into one-carbon metabolism","volume":"548","author":"Burgos-Barragan","year":"2017","journal-title":"Nature"},{"key":"2024081200022947100_B3","doi-asserted-by":"crossref","first-page":"101850","DOI":"10.1016\/j.redox.2020.101850","article-title":"The toxic side of one-carbon metabolism and epigenetics","volume":"40","author":"Morellato","year":"2021","journal-title":"Redox. 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