Hypoxia-induced SETX links replication stress with the unfolded protein response

• DOI: 10.1038/s41467-021-24066-z
• Publication Date: 2021-06-17T10:03:09Z
• Authors: Shaliny Ramachandran; Tiffany S. Ma; Jon Griffin; Natalie Ng; Iosifina P. Foskolou; Ming-Shih Hwang; Pedro Victori; Wei-Chen Cheng; Francesca M. Buffa; Katarzyna B. Lesz...; Sherif F. El-Khamisy; Natalia Gromak; Ester M. Hammond
• Keywords: ATF4; Transcription; Hypoxia; Integrated stress response

Abstract Tumour hypoxia is associated with poor patient prognosis and therapy resistance. A unique transcriptional response initiated by which includes the rapid activation of numerous transcription factors in a background reduced global transcription. Here, we show that biological to accumulation R-loops induction RNA/DNA helicase SETX. In absence hypoxia-induced SETX, R-loop levels increase, DNA damage accumulates, replication rates decrease. Therefore, suggesting that, SETX plays role protecting cells from induced during hypoxia. Importantly, propose mechanism reliant on PERK/ATF4 arm unfolded protein response. These data not only highlight cellular hypoxia, both stress-dependent an but uncover novel link between these two distinct pathways.