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.
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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!« Back To Main