INNATE IMMUNITY

Signaling to senescence

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Science  25 Aug 2017:
Vol. 357, Issue 6353, pp. 769-770
DOI: 10.1126/science.357.6353.769-d

“Damage-induced” senescence is a key component of many distinct physiological and pathological processes including cancer, aging, and wound healing. The detection of cytosolic DNA by cyclic GMP-AMP synthase (cGAS) is a key strategy by which the innate immune system senses the presence of pathogens. Activation of cGAS can also be evoked by self-DNA. Glück et al. found that cGAS detects cytosolic DNA fragments in stressed proliferating cells, which triggers cell cycle arrest and enforces premature senescence. Multiple distinct stimuli of cellular senescence engaged cGAS signaling in vitro. Furthermore, irradiated mice exhibited a cGAS-dependent senescence response in the liver and lung. Thus, in addition to its role in antiviral defense, cGAS is a cell-intrinsic sensor of DNA replication stress that protects against unconstrained proliferation of damaged cells.

Nat. Cell Biol. 10.1038/ncb3586 (2017).

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