期刊
NATURE COMMUNICATIONS
卷 12, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-021-24066-z
关键词
-
资金
- CRUK grant [C5255/A23755]
- MRC studentship [MC_ST_U16007]
- CRUK Oxford Centre Prize [C38302/A12981]
- CRUK [23969]
- Wellcome Trust Investigator Award [103844]
- Lister Institute of Preventative Medicine Fellowship [137661]
- Jean Shanks Foundation/ Pathological Society of Great Britain and Ireland Clinical PhD Fellowship [JSPS CPhD 2018 01]
- Royal Society University Research fellowship
Hypoxia induces a unique cellular transcriptional response, including the accumulation of R-loops and the induction of the RNA/DNA helicase SETX. SETX plays a critical role in protecting cells from DNA damage induced during transcription in hypoxia, and its induction mechanism in hypoxia relies on the PERK/ATF4 arm of the unfolded protein response.
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. Hypoxia induces a change in transcriptional response in mammalian cells. Here the authors reveal a role for the RNA/DNA helicase Senataxin in protecting cells from DNA damage induced during transcription in hypoxia.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据