Advancing the understanding of endogenous DNA double-strand breaks

DNA double-strand breaks (DSBs) jeopardize genome integrity and might give rise to structural rearrangements associated with cancer, when repaired unfaithfully. In a new study led by SciLifeLab researcher Nicola Crosetto (Karolinska Institutet), a research team delves deeper into the matter.

While exogenous agents such as chemotherapy and ionizing radiation can invoke the DSBs, a large amount of the breakages occur during vital endogenous DNA transactions such as replication and transcription. In the research group’s paper, published in Genes, they discuss the mechanisms of endogenous DSB formation, the trade-off between essential DNA transactions and the challenges these processes impose on genomic integrity. They also highlight the emerging methods for genome-wide profiling of DSBs and reflect on future research directions that can help advance our understanding of DSB formation and repair.

“In the years to come, to deepen our understanding of variation in DSB susceptibility and cellular implications, integrative approaches will be needed to help decipher how genome-wide landscapes of endogenous DSBs […] are shaped by and/or shape the underlying transcriptome, epigenome, 3D genome, and, possibly, the compartmentalized context of the nucleus”, the researchers write in their paper.

Read the full paper in Genes