Endogenous DNA damage is a major contributor to mutations, which are drivers of
cancer development. Bromodomain (BRD)
proteins are well-established participants in
chromatin-based DNA damage response (DDR) pathways, which maintain genome integrity from cell-intrinsic and extrinsic
DNA-damaging sources. BRD
proteins are most well-studied as regulators of transcription, but emerging evidence has revealed their importance in other
DNA-templated processes, including DNA repair and replication. How BRD
proteins mechanistically protect cells from endogenous DNA damage through their participation in these pathways remains an active area of investigation. Here, we review several recent studies establishing BRD
proteins as key influencers of endogenous DNA damage, including
DNA-
RNA hybrid (R-loops) formation during transcription and participation in replication stress responses. As endogenous DNA damage is known to contribute to several human diseases, including neurodegeneration, immunodeficiencies,
cancer, and aging, the ability of BRD
proteins to suppress DNA damage and mutations is likely to provide new insights into the involvement of BRD
proteins in these diseases. Although many studies have focused on BRD
proteins in transcription, evidence indicates that BRD
proteins have emergent functions in DNA repair and
genome stability and are participants in the etiology and treatment of diseases involving endogenous DNA damage.