Janeway, C. A. Jr Approaching the asymptote? Evolution and revolution in immunology. Cold Spring Harb. Symp. Quant. Biol. 54, 1–13 (1989).

Article  CAS  PubMed  Google Scholar 

Matzinger, P. Tolerance, danger, and the extended family. Annu. Rev. Immunol. 12, 991–1045 (1994).

Article  CAS  PubMed  Google Scholar 

Land, W. Allograft injury mediated by reactive oxygen species: from conserved proteins of Drosophila to acute and chronic rejection of human transplants. Part III: interaction of (oxidative) stress-induced heat shock proteins with toll-like receptor-bearing cells of innate immunity and its consequences for the development of acute and chronic allograft rejection. Transplant. Rev. 17, 67–86 (2003). This paper represents the first description of the concept of damage-associated molecular patterns (DAMPs).

Article  Google Scholar 

Chen, G. Y. & Nunez, G. Sterile inflammation: sensing and reacting to damage. Nat. Rev. Immunol. 10, 826–837 (2010).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gong, T., Liu, L., Jiang, W. & Zhou, R. DAMP-sensing receptors in sterile inflammation and inflammatory diseases. Nat. Rev. Immunol. 20, 95–112 (2020).

Article  CAS  PubMed  Google Scholar 

Roh, J. S. & Sohn, D. H. Damage-associated molecular patterns in inflammatory diseases. Immune Netw. 18, e27 (2018).

Article  PubMed  PubMed Central  Google Scholar 

Kaur, J., Singh, H. & Naqvi, S. Intracellular DAMPs in neurodegeneration and their role in clinical therapeutics. Mol. Neurobiol. 60, 3600–3616 (2023).

Article  CAS  PubMed  Google Scholar 

Wang, X. & Labzin, L. I. Inflammatory cell death: how macrophages sense neighbouring cell infection and damage. Biochem. Soc. Trans. 51, 303–313 (2023).

Article  PubMed  PubMed Central  Google Scholar 

Shim, Y.-R. & Jeong, W.-I. Recent advances of sterile inflammation and inter-organ cross-talk in alcoholic liver disease. Exp. Mol. Med. 52, 772–780 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bai, J. & Liu, F. Nuclear cGAS: sequestration and beyond. Protein Cell 13, 90–101 (2021).

Article  PubMed  PubMed Central  Google Scholar 

Briard, B., Place, D. E. & Kanneganti, T.-D. DNA sensing in the innate immune response. Physiology 35, 112–124 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chen, M., Linstra, R. & van Vugt, M. Genomic instability, inflammatory signaling and response to cancer immunotherapy. Biochim. Biophys. Acta Rev. Cancer 1877, 188661 (2022).

Article  CAS  PubMed  Google Scholar 

Volkman, H. E., Cambier, S., Gray, E. E. & Stetson, D. B. Tight nuclear tethering of cGAS is essential for preventing autoreactivity. eLife 8, e47491 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gentili, M. et al. The N-terminal domain of cGAS determines preferential association with centromeric DNA and innate immune activation in the nucleus. Cell Rep. 26, 2377–2393.e2313 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Michalski, S. et al. Structural basis for sequestration and autoinhibition of cGAS by chromatin. Nature 587, 678–682 (2020).

Article  CAS  PubMed  Google Scholar 

Pathare, G. R. et al. Structural mechanism of cGAS inhibition by the nucleosome. Nature 587, 668–672 (2020).

Article  CAS  PubMed  Google Scholar 

Zhao, B. et al. The molecular basis of tight nuclear tethering and inactivation of cGAS. Nature 587, 673–677 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Boyer, J. A. et al. Structural basis of nucleosome-dependent cGAS inhibition. Science 370, 450–454 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kujirai, T. et al. Structural basis for the inhibition of cGAS by nucleosomes. Science 370, 455–458 (2020). This paper, together with Michalski et al. (2020), Pathare et al. (2020), Zhao et al. (2020) and Boyer et al. (2020), provides the key mechanism of how nucleosomes inhibit nuclear cGAS activation, explaining why nuclear cGAS does not recognize genomic self DNA.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chen, H. et al. cGAS suppresses genomic instability as a decelerator of replication forks. Sci. Adv. 6, eabb8941 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Liu, H. et al. Nuclear cGAS suppresses DNA repair and promotes tumorigenesis. Nature 563, 131–136 (2018).

Article  CAS  PubMed  Google Scholar 

Zhen, Z. et al. Nuclear cGAS restricts L1 retrotransposition by promoting TRIM41-mediated ORF2p ubiquitination and degradation. Nat. Commun. 14, 8217 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wang, L., Wen, M. & Cao, X. Nuclear hnRNPA2B1 initiates and amplifies the innate immune response to DNA viruses. Science 365, eaav0758 (2019). This paper identifies hnRNPA2B1 as a nuclear receptor that recognizes DNA viruses and fulfils a crucial role in the antiviral innate immune response.

Article  CAS  PubMed  Google Scholar 

Zhang, X., Flavell, R. A. & Li, H.-B. hnRNPA2B1: a nuclear DNA sensor in antiviral Immunity. Cell Res. 29, 879–880 (2019).

Article  PubMed  PubMed Central  Google Scholar 

Liu, Y. et al. Structural insight into hnRNP A2/B1 homodimerization and DNA recognition. J. Mol. Biol. 435, 167920 (2023).

Article  CAS  PubMed  Google Scholar 

Bakhoum, S. F. et al. Chromosomal instability drives metastasis through a cytosolic DNA response. Nature 553, 467–472 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Coquel, F. et al. SAMHD1 acts at stalled replication forks to prevent interferon induction. Nature 557, 57–61 (2018).

Article  CAS  PubMed  Google Scholar 

Di Micco, A. et al. AIM2 inflammasome is activated by pharmacological disruption of nuclear envelope integrity. Proc. Natl Acad. Sci. USA 113, E4671–E4680 (2016).

Article  PubMed  PubMed Central  Google Scholar 

Krupina, K., Goginashvili, A. & Cleveland, D. W. Causes and consequences of micronuclei. Curr. Opin. Cell Biol. 70, 91–99 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Decout, A., Katz, J. D., Venkatraman, S. & Ablasser, A. The cGAS–STING pathway as a therapeutic target in inflammatory diseases. Nat. Rev. Immunol. 21, 548–569 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Li, T. & Chen, Z. J. The cGAS–cGAMP–STING pathway connects DNA damage to inflammation, senescence, and cancer. J. Exp. Med. 215, 1287–1299 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Martin, S. K., Tomida, J. & Wood, R. D. Disruption of DNA polymerase zeta engages an innate immune response. Cell Rep. 34, 108775 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bartsch, K. et al. Absence of RNase H2 triggers generation of immunogenic micronuclei removed by autophagy. Hum. Mol. Genet. 26, 3960–3972 (2017).

Article  CAS  PubMed  Google Scholar 

Gratia, M. et al. Bloom syndrome protein restrains innate immune sensing of micronuclei by cGAS. J. Exp. Med. 216, 1199–1213 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Orr, B. et al. An anaphase surveillance mechanism prevents micronuclei formation from frequent chromosome segregation errors. Cell Rep. 37, 109783 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mohr, L. et al. ER-directed TREX1 limits cGAS activation at micronuclei. Mol. Cell 81, 724–738.e729 (2021).

Article  CAS  PubMed  PubMed Central