Fig. 7: A proposed model for KLF5’s role in protecting cells against transcription-dependent replication stress.
From: KLF5 loss sensitizes cells to ATR inhibition and is synthetic lethal with ARID1A deficiency
Top: KLF5 binds DNA and facilitates BRD4 recruitment to chromatin, thus regulating RNAPII promoter-proximal pausing and transcription elongation in a manner that prevents transcription-associated DNA replication stress. Bottom: Upon KLF5 loss, the recruitment of BRD4 to chromatin is disrupted, causing increased transcription-replication conflicts and downstream events such as DNA replication stress, DNA damage, and increased R-loop accumulation, which when combined with ATR inhibition or with ARID1A deficiency, causes genomic instability and cell death. Created in BioRender. Diab, S. (2025) https://BioRender.com/r68r668.
