NIH R01 · 2025
Mechanisms of R-loop-Associated Genome Instability
PROJECT SUMMARY Maintaining genome integrity is paramount for all cells, yet the essential cellular process of gene transcription introduces myriad opportunities for cells to incur damage to their genome. For example, transcription can lead to the formation of R-loops, three-stranded structures that contain an RNA-DNA hybrid and a region of single- stranded DNA. R-loops occur throughout the genome of mammalian cells and regulate various aspects of gene expression. They are typically dynamic, but some sequences and cellular perturbations can lead to stable R-loops that can stall transcription, block DNA replication, or cause DNA breaks via incompletely understood mechanisms. Moreover, some…
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