2026-05-22T00:51:50Zhttps://repisalud.isciii.es/rest/oai/request
oai:repisalud.isciii.es:20.500.12105/122792024-11-29T13:26:18Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud author Visnes, Torkild author Benítez-Buelga, Carlos author Cázares-Körner, Armando author Sanjiv, Kumar author Hanna, Bishoy M F author Mortusewicz, Oliver author Rajagopal, Varshni author Albers, Julian J author Hagey, Daniel W author Bekkhus, Tove author Eshtad, Saeed author Baquero, Juan Miguel author Masuyer, Geoffrey author Wallner, Olov author Müller, Sarah author Pham, Therese author Göktürk, Camilla author Rasti, Azita author Suman, Sharda author Raul, Torres-Ruiz author Sarno, Antonio author Wiita, Elisée author Homan, Evert J author Karsten, Stella author Marimuthu, Karthick author Michel, Maurice author Koolmeister, Tobias author Scobie, Martin author Loseva, Olga author Almlöf, Ingrid author Unterlass, Judith Edda author Pettke, Aleksandra author Boström, Johan author Pandey, Monica author Gad, Helge author Herr, Patrick author Jemth, Ann-Sofie author El Andaloussi, Samir author Kalderén, Christina author Rodriguez-Perales, Sandra author Benítez, Javier author Krokan, Hans E author Altun, Mikael author Stenmark, Pål author Berglund, Ulrika Warpman author Helleday, Thomas author Rodriguez Perales, Sandra author El Andaloussi, Samir funder Instituto de Salud Carlos III funder Unión Europea 2021-03-16T08:34:58Z 2021-03-16T08:34:58Z 2020 Nucleic Acids Res . 2020 ;48(21):12234-12251. 10.1093/nar/gkaa1048 1362-4962 0305-1048 Nucleic acids research 33211885 http://hdl.handle.net/20.500.12105/12279 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. eng Targeting OGG1 arrests cancer cell proliferation by inducing replication stress. journal article 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 URL https://repisalud.isciii.es/bitstreams/15e2ad60-d3ac-477e-b4ac-8c887490f0d5/download File MD5 27c44391684cb46c7c0a72a00d030997 4179338 application/pdf TargetingOGG1arrestscancer_2020.pdf URL https://repisalud.isciii.es/bitstreams/ae7ff7d0-b245-476c-870c-94fd2ba0981c/download File MD5 66bb7e7db88a9ab4c5043cb1d7716bf1 2073418 application/pdf gkaa1048_supplemental_file.pdf URL https://repisalud.isciii.es/bitstreams/16def40e-6652-4d75-b15b-662203fce7bb/download File MD5 b0f932fa758cfe96d7a43a50a0f9388e 92769 text/plain TargetingOGG1arrestscancer_2020.pdf.txt URL https://repisalud.isciii.es/bitstreams/9d00e419-7f58-4e55-b6b8-16e4e4b1c3ec/download File MD5 2e1bcd21547cbc7b8432078869475dc2 15589 text/plain gkaa1048_supplemental_file.pdf.txt