The LUMINIDEPENDENS protein is a general repressor of transcription in Arabidopsis

Genomic integrity is constantly challenged by transcription/replication conflicts (TRCs), a major source of replication stress (RS) and instability across all life forms. While extensive studies have uncovered TRC resolution mechanisms in animals, yeast, and prokaryotes, their counterparts in plants remain largely unexplored. Through a forward genetic screen, we identified the LUMINIDEPENDENS (LD) protein, previously known for regulating the flowering repressor FLC, as a key player in mitigating RS in plants. Strikingly, transcriptomic analyses reveal that loss of LD results in the upregulation of over 13,000 genes, establishing LD as a global transcriptional repressor. Consistent with this role, LD binds a substantial portion of the Arabidopsis genome, and interacts with the MED18 subunit of the Mediator complex to modulate RNA polymerase II phosphorylation. These findings uncover a fundamental function of LD in fine-tuning transcription genome-wide, with an additional role in suppressing TRCs by locally dampening transcription and promoting replication fork progression. Our work highlights a previously unrecognized genome-protective strategy in plants, opening new avenues for understanding TRC management in eukaryotic systems.