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Targeting OGG1 arre...
Targeting OGG1 arrests cancer cell proliferation by inducing replication stress
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- Visnes, Torkild (author)
- Karolinska Institute
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Benitez-Buelga, Carlos (author)
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Cázares-Körner, Armando (author)
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- Sanjiv, Kumar (author)
- Karolinska Institutet
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- Hanna, Bishoy M. F. (author)
- Karolinska Institutet
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- Mortusewicz, Oliver (author)
- Karolinska Institutet
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Rajagopal, Varshni (author)
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Albers, Julian J. (author)
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- Hagey, Daniel W. (author)
- Karolinska Institutet
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Bekkhus, Tove (author)
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Eshtad, Saeed (author)
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- Baquero, Juan Miguel (author)
- Spanish National Cancer Research Center (CNIO)
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- Masuyer, Geoffrey (author)
- Stockholm University,Stockholms universitet,Institutionen för biokemi och biofysik
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- Wallner, Olov (author)
- Karolinska Institutet
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Müller, Sarah (author)
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- Pham, Therese (author)
- Karolinska Institutet
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Göktürk, Camilla (author)
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Rasti, Azita (author)
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- Suman, Sharda (author)
- Karolinska Institutet
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- Torres-Ruiz, Raúl (author)
- University of Barcelona
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- Sarno, Antonio (author)
- Norwegian University of Science and Technology
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- Wiita, Elisée (author)
- Karolinska Institutet
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- Homan, Evert J. (author)
- Karolinska Institutet
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Karsten, Stella (author)
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Marimuthu, Karthick (author)
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- Michel, Maurice (author)
- Karolinska Institutet
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- Koolmeister, Tobias (author)
- Karolinska Institutet
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Scobie, Martin (author)
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Loseva, Olga (author)
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- Almlöf, Ingrid (author)
- Karolinska Institutet
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Unterlass, Judith Edda (author)
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- Pettke, Aleksandra (author)
- Karolinska Institutet
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Boström, Johan (author)
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- Pandey, Monica (author)
- Sheffield Hallam University
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- Gad, Helge (author)
- Karolinska Institutet
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- Herr, Patrick (author)
- Sheffield Hallam University
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Jemth, Ann-Sofie (author)
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El Andaloussi, Samir (author)
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- Kalderén, Christina (author)
- Karolinska Institutet
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Rodriguez-Perales, Sandra (author)
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- Benitez, Javier (author)
- Spanish National Cancer Research Center (CNIO)
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- Krokan, Hans E. (author)
- Norwegian University of Science and Technology
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Altun, Mikael (author)
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- Stenmark, Pål (author)
- Stockholm University,Lund University,Lunds universitet,Stockholms universitet,Institutionen för biokemi och biofysik,Strukturell biokemi,Forskargrupper vid Lunds universitet,Structural Biochemistry,Lund University Research Groups
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- Warpman Berglund, Ulrika (author)
- Karolinska Institutet
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- Helleday, Thomas (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2020-11-19
- 2020
- English.
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In: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 48:21, s. 12234-12251
- Related links:
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https://doi.org/10.1...
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https://doi.org/10.1...
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http://dx.doi.org/10... (free)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://lup.lub.lu.s...
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Abstract
Subject headings
Close
- 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.
Subject headings
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Visnes, Torkild
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Benitez-Buelga, ...
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Cázares-Körner, ...
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Sanjiv, Kumar
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Hanna, Bishoy M. ...
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Mortusewicz, Oli ...
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show more...
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Rajagopal, Varsh ...
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Albers, Julian J ...
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Hagey, Daniel W.
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Bekkhus, Tove
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Eshtad, Saeed
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Baquero, Juan Mi ...
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Masuyer, Geoffre ...
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Wallner, Olov
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Müller, Sarah
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Pham, Therese
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Göktürk, Camilla
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Rasti, Azita
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Suman, Sharda
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Torres-Ruiz, Raú ...
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Sarno, Antonio
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Wiita, Elisée
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Homan, Evert J.
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Karsten, Stella
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Marimuthu, Karth ...
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Michel, Maurice
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Koolmeister, Tob ...
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Scobie, Martin
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Loseva, Olga
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Almlöf, Ingrid
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Unterlass, Judit ...
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Pettke, Aleksand ...
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Boström, Johan
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Pandey, Monica
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Gad, Helge
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Herr, Patrick
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Jemth, Ann-Sofie
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El Andaloussi, S ...
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Kalderén, Christ ...
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Rodriguez-Perale ...
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Benitez, Javier
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Krokan, Hans E.
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Altun, Mikael
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Stenmark, Pål
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Warpman Berglund ...
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Helleday, Thomas
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- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
- Articles in the publication
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Nucleic Acids Re ...
- By the university
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Stockholm University
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Lund University
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Karolinska Institutet