Transcription, though an essential process for all organisms, can promote genomic instability. I am investigating how transcription through repetitive regions of the genome affects chromosome fragility and genome instability. Repetitive sequences have the ability to form secondary DNA structures that can serve as barriers to replication and transcription machinery, leading to fork stalling and collisions that further promote genome instability and chromosome breakage. This chromosome breakage can lead to rearrangements and other genomic changes. I am specifically examining transcription through CAG repeats; CAG repeat expansion is associated with Huntington’s disease; and AT repeats at the common fragile site FRA16D.