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Targeting OGG1 arrests cancer cell proliferation by inducing replication stress



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.
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Academic article


  • Research Council of Norway (RCN) / 303369




  • Torkild Visnes
  • Carlos Benitez-Buelga
  • Armando Cázares-Körner
  • Kumar Sanjiv
  • Bishoy M F Hanna
  • Oliver Mortusewicz
  • Varshni Rajagopal
  • Julian J. Albers
  • Daniel W. Hagey
  • Tove Bekkhus
  • Saeed Eshtad
  • Juan Miguel Baquero
  • Geoffrey Masuyer
  • Olov Wallner
  • Sarah Müller
  • Therese Pham
  • Camilla Gokturk
  • Azita Rasti
  • Sharda Suman
  • Raúl Torres-Ruiz
  • Antonio Sarno
  • Elisée Wiita
  • Evert Homan
  • Stella Karsten
  • Karthick Marimuthu
  • M Michel
  • Tobias Koolmeister
  • Martin Scobie
  • Olga Loseva
  • Ingrid Almlöf
  • Judith Edda Unterlass
  • Aleksandra Pettke
  • Johan Boström
  • Monica Pandey
  • Helge Gad
  • Patrick Herr
  • Ann-Sofie Jemth
  • Samir El Andaloussi
  • Christina Kalderén
  • Sandra Rodriguez-Perales
  • Javier Benítez
  • Hans Einar Krokan
  • Mikael Altun
  • Pål Stenmark
  • Ulrika Warpman Berglund
  • Thomas Helleday


  • SINTEF Industry / Biotechnology and Nanomedicine
  • Karolinska Institutet
  • Spanish National Cancer Research Centre
  • Stockholm University
  • University of Bath
  • University of Barcelona
  • Norwegian University of Science and Technology
  • Helse Midt-Norge
  • SINTEF Ocean / Fisheries and New Biomarine Industry
  • University of Sheffield
  • Centro de Investigación Biomédica en Red
  • Lund University



Published in

Nucleic Acids Research (NAR)




Oxford University Press






12234 - 12251

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