Interaction of OGG1 with NKX3.1 due to oxidative DNA damage

8-Oxoguanine DNA glycosylase 1 (OGG1) is a member of base excision repair, responsible for the repair of 8-oxoG base damage induced by reactive oxygen species. As oxidative DNA damage contributes to prostate carcinogenesis, investigating the interaction of OGG1 with prostate-specific proteins, which function in DNA damage and repair mechanisms in prostate cells, is important to determine appropriate therapeutic targets and ultimately support the cancer treatment strategies. Therefore, in this study we investigated the protein-protein interaction of OGG1 with androgen receptor (AR), which is critical for prostate cell proliferation as well as NKX3.1, which is a tumor suppressor protein specific to prostate cells. In addition, S326C, a polymorphic variant of OGG1 formed by a single amino acid change, has been reported in literature to cause a deficiency in repair activity leading OGG1 to be a predisposition factor for prostate cancer. In our immunoprecipitation results, OGG1 was detected to physically interact with NKX3.1 and AR upon increased oxidative DNA damage by menadione treatment. Further, immunofluorescence microscopy results showed that OGG1 localizes in the nuclear speckles at basal and induced level of DNA damage. Although NKX3.1 co-localize with OGG1 in the nucleus, localization of OGG1 was not observed in nuclear speckles in the presence of NKX3.1 possibly due to reduced oxidative DNA damage in NKX3.1 expressing cells. However, reduced physical association of OGG1-S326C variant form in comparison to wild type and further no co-localization of variant form with NKX3.1 was detected supporting the idea that OGG1-S326C variant form contributes to the prostate carcinogenesis.