Stephan Hamperl, Michael Bocek, Joshua Saldivar, Tomek Swigut, and Karlene Cimprich featured in Cell and recommended by F1000Prime
The recent publication of “Transcription-Replication Conflict Orientation Modulates R-Loop Levels and Activates Distinct DNA Damage Responses” by Stephan Hamperl, Michael Bocek, Joshua Saldivar, Tomek Swigut, and Karlene Cimprich were featured in a Cell Preview and recommended on F1000Prime.
To read the original Cell Preview article, please click here.
To read the original F1000Prime recommendation, please click here.
A summary of the paper is included below:
Conflicts between transcription and replication are a potent source of DNA damage. Co-transcriptional R-loops could aggravate such conflicts by creating an additional barrier to replication fork progression. Here, we use a defined episomal system to investigate how conflict orientation and R-loop formation influence genome stability in human cells. R-loops, but not normal transcription complexes, induce DNA breaks and orientation-specific DNA damage responses during conflicts with replication forks. Unexpectedly, the replisome acts as an orientation-dependent regulator of R-loop levels, reducing R-loops in the co-directional (CD) orientation but promoting their formation in the head-on (HO) orientation. Replication stress and deregulated origin firing increase the number of HO collisions leading to genome-destabilizing R-loops. Our findings connect DNA replication to R-loop homeostasis and suggest a mechanistic basis for genome instability resulting from deregulated DNA replication, observed in cancer and other disease states.
Congratulations to Stephan Hamperl, Michael Bocek, Joshua Saldivar, Tomek Swigut, and Dr. Cimprich!