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dc.contributor.authorVisnes, Torkild
dc.contributor.authorBenitez-Buelga, Carlos
dc.contributor.authorCázares-Körner, Armando
dc.contributor.authorSanjiv, Kumar
dc.contributor.authorHanna, Bishoy M F
dc.contributor.authorMortusewicz, Oliver
dc.contributor.authorRajagopal, Varshni
dc.contributor.authorAlbers, Julian J.
dc.contributor.authorHagey, Daniel W.
dc.contributor.authorBekkhus, Tove
dc.contributor.authorEshtad, Saeed
dc.contributor.authorBaquero, Juan Miguel
dc.contributor.authorMasuyer, Geoffrey
dc.contributor.authorWallner, Olov
dc.contributor.authorMüller, Sarah
dc.contributor.authorPham, Therese
dc.contributor.authorGokturk, Camilla
dc.contributor.authorRasti, Azita
dc.contributor.authorSuman, Sharda
dc.contributor.authorTorres-Ruiz, Raúl
dc.contributor.authorSarno, Antonio
dc.contributor.authorWiita, Elisée
dc.contributor.authorHoman, Evert
dc.contributor.authorKarsten, Stella
dc.contributor.authorMarimuthu, Karthick
dc.contributor.authorMichel, M
dc.contributor.authorKoolmeister, Tobias
dc.contributor.authorScobie, Martin
dc.contributor.authorLoseva, Olga
dc.contributor.authorAlmlöf, Ingrid
dc.contributor.authorUnterlass, Judith Edda
dc.contributor.authorPettke, Aleksandra
dc.contributor.authorBoström, Johan
dc.contributor.authorPandey, Monica
dc.contributor.authorGad, Helge
dc.contributor.authorHerr, Patrick
dc.contributor.authorJemth, Ann-Sofie
dc.contributor.authorEl Andaloussi, Samir
dc.contributor.authorKalderén, Christina
dc.contributor.authorRodriguez-Perales, Sandra
dc.contributor.authorBenítez, Javier
dc.contributor.authorKrokan, Hans Einar
dc.contributor.authorAltun, Mikael
dc.contributor.authorStenmark, Pål
dc.contributor.authorBerglund, Ulrika Warpman
dc.contributor.authorHelleday, Thomas
dc.date.accessioned2021-01-21T11:07:11Z
dc.date.available2021-01-21T11:07:11Z
dc.date.created2020-11-25T12:27:43Z
dc.date.issued2020
dc.identifier.citationNucleic Acids Research. 2020, 48 (21), 12234-12251.en_US
dc.identifier.issn0305-1048
dc.identifier.urihttps://hdl.handle.net/11250/2724083
dc.description.abstractAbstract Altered oncogene expression in cancer cells causes loss of redox homeostasis resulting in oxidative DNA damage, e.g. 8-oxoguanine (8-oxoG), repaired by base excision repair (BER). PARP1 coordinates BER and relies on the upstream 8-oxoguanine-DNA glycosylase (OGG1) to recognise and excise 8-oxoG. Here we hypothesize that OGG1 may represent an attractive target to exploit reactive oxygen species (ROS) elevation in cancer. Although OGG1 depletion is well tolerated in non-transformed cells, we report here that OGG1 depletion obstructs A3 T-cell lymphoblastic acute leukemia growth in vitro and in vivo, validating OGG1 as a potential anti-cancer target. In line with this hypothesis, we show that OGG1 inhibitors (OGG1i) target a wide range of cancer cells, with a favourable therapeutic index compared to non-transformed cells. Mechanistically, OGG1i and shRNA depletion cause S-phase DNA damage, replication stress and proliferation arrest or cell death, representing a novel mechanistic approach to target cancer. This study adds OGG1 to the list of BER factors, e.g. PARP1, as potential targets for cancer treatment.en_US
dc.language.isoengen_US
dc.publisherOxford Academicen_US
dc.relation.urihttps://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkaa1048/5992293
dc.rightsNavngivelse 4.0 Internasjonal*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/deed.no*
dc.titleTargeting OGG1 arrests cancer cell proliferation by inducing replication stressen_US
dc.typePeer revieweden_US
dc.typeJournal articleen_US
dc.description.versionpublishedVersionen_US
dc.source.pagenumber12234-12251en_US
dc.source.volume48en_US
dc.source.journalNucleic Acids Researchen_US
dc.source.issue21en_US
dc.identifier.doi10.1093/nar/gkaa1048
dc.identifier.cristin1852178
dc.relation.projectSINTEF AS: 102020885en_US
dc.relation.projectNorges forskningsråd: 303369en_US
dc.description.localcodeC The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.en_US
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode2


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