{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T12:10:55Z","timestamp":1790770255202,"version":"4.1.0"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T00:00:00Z","timestamp":1634083200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100000855","name":"University of Birmingham","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000855","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Maastricht"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,11,29]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Reactive oxygen species formation and resultant oxidative damage to DNA are ubiquitous events in cells, the homeostasis of which can be dysregulated in a range of pathological conditions. Base excision repair (BER) is the primary repair mechanism for oxidative genomic DNA damage. One prevalent oxidised base modification, 8-oxoguanine (8-oxoG), is recognised by 8-oxoguanine glycosylase-1 (OGG1) initiating removal and repair via BER. Surprisingly, Ogg1 null mouse embryonic fibroblasts (mOgg1\u2212\/\u2212 MEFs) do not accumulate 8-oxoG in the genome to the extent expected. This suggests that there are backup repair mechanisms capable of repairing 8-oxoG in the absence of OGG1. In the current study, we identified components of NER (Ercc1, Ercc4, Ercc5), BER (Lig1, Tdg, Nthl1, Mpg, Mgmt, NEIL3), MMR (Mlh1, Msh2, Msh6) and DSB (Brip1, Rad51d, Prkdc) pathways that are transcriptionally elevated in mOgg1\u2212\/\u2212 MEFs. Interestingly, all three nucleotide excision repair genes identified: Ercc1 (2.5 \u00b1 0.2-fold), Ercc4 (1.5 \u00b1 0.1-fold) and Ercc5 (1.7 \u00b1 0.2-fold) have incision activity. There was also a significant functional increase in NER activity (42.0 \u00b1 7.9%) compared to WT MEFs. We also observed upregulation of both Neil3 mRNA (37.9 \u00b1 1.6-fold) and protein in mOgg1\u2212\/\u2212 MEFs. This was associated with a 3.4 \u00b1 0.4-fold increase in NEIL3 substrate sites in genomic DNA of cells treated with BSO, consistent with the ability of NEIL3 to remove 8-oxoG oxidation products from genomic DNA. In conclusion, we suggest that in Ogg1-null cells, upregulation of multiple DNA repair proteins including incision components of the NER pathway and Neil3 are important compensatory responses to prevent the accumulation of genomic 8-oxoG.<\/jats:p>","DOI":"10.1093\/mutage\/geab038","type":"journal-article","created":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T01:30:33Z","timestamp":1634088633000},"page":"437-444","source":"Crossref","is-referenced-by-count":9,"title":["Upregulation of mNEIL3 in<i>Ogg1<\/i>-null cells is a potential backup mechanism for 8-oxoG repair"],"prefix":"10.1093","volume":"36","author":[{"given":"Ellen B","family":"Higgs","sequence":"first","affiliation":[{"name":"School of Biosciences, The University of Birmingham, Birmingham, UK"},{"name":"Department of Pharmacology & Toxicology, School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Godschalk","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Toxicology, School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine A S","family":"Langie","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Toxicology, School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederik-Jan","family":"van Schooten","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Toxicology, School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolas J","family":"Hodges","sequence":"additional","affiliation":[{"name":"School of Biosciences, The University of Birmingham, Birmingham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,10,13]]},"reference":[{"key":"2021120108360192700_CIT0001","first-page":"1","article-title":"Review of mammalian DNA repair and translational implications","volume":"295","author":"Hansen","year":"2000","journal-title":"J. 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