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

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. Leszczynska, Sherif F. El-Khamisy, Natalia Gromak and Ester M. Hammond ()
Additional contact information
Shaliny Ramachandran: University of Oxford
Tiffany S. Ma: University of Oxford
Jon Griffin: University of Sheffield
Natalie Ng: University of Oxford
Iosifina P. Foskolou: University of Oxford
Ming-Shih Hwang: University of Oxford
Pedro Victori: University of Oxford
Wei-Chen Cheng: University of Oxford
Francesca M. Buffa: University of Oxford
Katarzyna B. Leszczynska: University of Oxford
Sherif F. El-Khamisy: University of Sheffield
Natalia Gromak: University of Oxford
Ester M. Hammond: University of Oxford

Nature Communications, 2021, vol. 12, issue 1, 1-14

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

Date: 2021
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-021-24066-z Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24066-z

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-24066-z

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().