Dear All

It is my pleasure to announce that this Friday, 2nd December, at 3pm in our CN lecture hall, we will host prof. Prof. Ester M. Hammond from the Department of Oncology at the University of Oxford.

Prof. Hammond will give a lecture entitled: Hypoxia-induced ROS leads to the accumulation of R-loops independently of DNA damage.

Abstract

Hypoxia is a common feature of solid tumours and is associated with poor patient prognosis and therapy resistance. Severe hypoxia (<0.1% O 2 ) is one of the few physiologically relevant stresses that activates both the DNA damage/replication stress response and the unfolded protein response (UPR). Recently, we demonstrated that hypoxia-induced replication stress includes the accumulation of R-loops despite a decrease in global transcription rates in the same conditions. Interestingly, we found that the RNA/DNA helicase SETX, which resolves R-loops, was induced in hypoxic conditions and that this occurred in a UPR-dependent manner. These findings led us to question both the mechanism and consequence of hypoxia-induced R-loops. Here, we show that hypoxia-induced R-loops regulate the nucleolar stress response. Specifically, R-loops accumulate on the rDNA in hypoxia and contribute to reduced rDNA transcription in hypoxic conditions. The nucleolar stress protein nucleolin translocates from the nucleolus to the nucleoplasm in hypoxia, and this translocation is also dependent on R-loops. Furthermore, we determined that the accumulation of R-loops in hypoxia is dependent on reactive oxygen species (ROS) as ROS scavengers partially rescued rDNA transcription repression and nucleolin translocation. Together, these data led us to hypothesise that the hypoxic UPR, in an attempt to shut own protein synthesis, also downregulates the production of ribosomes, an energy-demanding process, through the ROS-dependent accumulation of R-loops at the rDNA.

The seminar will be followed by a get together.

With best wishes
Aleksandra Pękowska