Breast Tumorigenesis Associated with BRCA1 Deficiency is Dependent on RNF8

Defects in DNA damage repair result in genomic instability; a process that has been recognized as a driving factor in the development of several types of cancer. RNF8 and BRCA1 are E3 ubiquitin ligases that play crucial roles as tumor suppressors by mediating cellular responses to DNA double strand breaks (DSBs). In animal models, we have found that Rnf8 and Brca1 deficiencies predispose mice to the development of mammary tumors. Interestingly, Rnf8-/-;WapCre;Brca1fl/fl double mutant mice are protected from mammary tumorigenesis. Data collected in this study suggests that Rnf8-/- ;WapCre;Brca1fl/fl double mutant mice are protected from tumorigenesis due to a unique synthetic lethal-like interaction between RNF8/Rnf8 and BRCA1/Brca1. We propose that RNF8 inhibition should be investigated further as a potential therapeutic target for the treatment of BRCA1-associated breast cancer.M.Sc.2020-11-15 00:00:0