Fragile DNA in development

Eukaryotic DNA exists in a wound-up state. Imagine two ropes that you intertwined tightly, but now you want to unwind just the middle part. This is a problem cells face daily during replication and transcription. To enable these important biological processes, DNA helicase can unwind the DNA at specific points. However, there has also been some speculation that DNA double-strand breaks (DSBs) contribute to unwinding of DNA, too. These breaks are like cuts in the intertwined ropes: if you leave the ends dangling, they will unwind. But DSBs are difficult to detect and so remain under-researched.

To explain the role of DSBs in genome regulation the Crosetto group has developed breaks labeling in situ and sequencing (BLISS). With this technique DSBs can be detected in a homogeneous pool of cells. This project leveraged this approach to understand whether DSBs, and therefore DNA fragility, plays a role in the development of neurons. I used BLISS data from a differentiation time-course to show that DNA fragility changes across neuronal development and. Fragility also seemed to have some association with transcription, although some questions remained. Overall, this project provided novel insights into the role of DNA fragility in normal human cells.