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

ABSTRACT: Study of Transcriptomic changes upon Senataxin depletion in Normoxia and Hypoxia

ORGANISM(S): Homo sapiens

PROVIDER: GSE157371 | GEO | 2021/04/26

REPOSITORIES: GEO

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

Project description: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.

| S-EPMC8211819 | biostudies-literature

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

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

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Gene expression profiling in Setx shRNA P19 cells, wild type human Setx P19 transfected cells with and without retionoic acid

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