BAP1 is phosphorylated at serine 592 in S-phase following DNA damage

•BAP1 is phosphorylated at Ser592 (pS592) following DNA damage or replication stress.•Phosphorylation of BAP1 is rapid and occurs in S-phase to a small fraction of BAP1.•In contrast to the majority of BAP1, pS592-BAP1 is not associated with chromatin. The human BAP1 deubiquitinating enzyme is a chromatin-bound transcriptional regulator and tumor suppressor. BAP1 functions in suppressing cell proliferation, yet its role in the DNA damage response pathway is less understood. In this study we characterized DNA damage-induced phosphorylation of BAP1 at serine 592 (pS592) and the cellular outcomes of this modification. In contrast to the majority of BAP1, pS592-BAP1 is predominantly dissociated from chromatin. Our findings support a model whereby stress induced phosphorylation functions to displace BAP1 from specific promoters. We hypothesize that this regulates the transcription of a subset of genes involved in the response to DNA damage. HCF-1physically interacts with Bap1 by anti bait coimmunoprecipitation (1, 2)