1 Woo, S.R., Corrales, L. & Gajewski, T.F. The STING pathway and the T cell-inflamed tumor microenvironment. Trends Immunol. 36, 250–256 (2015).

2 Barber, G.N. STING: infection, inflammation and cancer. Nat. Rev. Immunol. 15, 760–770 (2015).

3 Ishikawa, H. & Barber, G.N. STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling. Nature 455, 674–678 (2008).

4 Ishikawa, H., Ma, Z. & Barber, G.N. STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity. Nature 461, 788–792 (2009).

5 Liu, S. et al. Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation. Science 347, aaa2630 (2015).

6 Sun, L., Wu, J., Du, F., Chen, X. & Chen, Z.J. Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science 339, 786–791 (2013).

7 Ahn, J., Konno, H. & Barber, G.N. Diverse roles of STING-dependent signaling on the development of cancer. Oncogene 34, 5302–5308 (2015).

8 Ohkuri, T. et al. STING contributes to antiglioma immunity via triggering type I IFN signals in the tumor microenvironment. Cancer Immunol. Res. 2, 1199–1208 (2014).

9 Xia, T., Konno, H., Ahn, J. & Barber, G.N. Deregulation of STING signaling in colorectal carcinoma constrains DNA damage responses and correlates with tumorigenesis. Cell Rep. 14, 282–297 (2016).

10 Woo, S.R. et al. STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors. Immunity 41, 830–842 (2014).

11 Klarquist, J. et al. STING-mediated DNA sensing promotes antitumor and autoimmune responses to dying cells. J. Immunol. 193, 6124–6134 (2014).

12 Bryan, T.M., Englezou, A., Dalla-Pozza, L., Dunham, M.A. & Reddel, R.R. Evidence for an alternative mechanism for maintaining telomere length in human tumors and tumor-derived cell lines. Nat. Med. 3, 1271–1274 (1997).

13 Kim, N.W. et al. Specific association of human telomerase activity with immortal cells and cancer. Science 266, 2011–2015 (1994).

14 Henson, J.D. et al. DNA C-circles are specific and quantifiable markers of alternative-lengthening-of-telomeres activity. Nat. Biotechnol. 27, 1181–1185 (2009).

15 Pickett, H.A. & Reddel, R.R. Molecular mechanisms of activity and derepression of alternative lengthening of telomeres. Nat. Struct. Mol. Biol. 22, 875–880 (2015).

16 Dilley, R.L. & Greenberg, R.A. ALTernative telomere maintenance and cancer. Trends Cancer 1, 145–156 (2015).

17 Groff-Vindman, C., Cesare, A.J., Natarajan, S., Griffith, J.D. & McEachern, M.J. Recombination at long mutant telomeres produces tiny single- and double-stranded telomeric circles. Mol. Cell. Biol. 25, 4406–4412 (2005).

18 Cesare, A.J. & Griffith, J.D. Telomeric DNA in ALT cells is characterized by free telomeric circles and heterogeneous t-loops. Mol. Cell. Biol. 24, 9948–9957 (2004).

19 Compton, S.A., Choi, J.H., Cesare, A.J., Ozgür, S. & Griffith, J.D. Xrcc3 and Nbs1 are required for the production of extrachromosomal telomeric circles in human alternative lengthening of telomere cells. Cancer Res. 67, 1513–1519 (2007).

20 Wang, R.C., Smogorzewska, A. & de Lange, T. Homologous recombination generates T-loop-sized deletions at human telomeres. Cell 119, 355–368 (2004).

21 Lin, C.Y. et al. Extrachromosomal telomeric circles contribute to Rad52-, Rad50- and polymerase delta-mediated telomere-telomere recombination in Saccharomyces cerevisiae. Eukaryot. Cell 4, 327–336 (2005).

22 Natarajan, S. & McEachern, M.J. Recombinational telomere elongation promoted by DNA circles. Mol. Cell. Biol. 22, 4512–4521 (2002).

23 Zellinger, B., Akimcheva, S., Puizina, J., Schirato, M. & Riha, K. Ku suppresses formation of telomeric circles and alternative telomere lengthening in Arabidopsis. Mol. Cell 27, 163–169 (2007).

24 Vannier, J.B., Pavicic-Kaltenbrunner, V., Petalcorin, M.I., Ding, H. & Boulton, S.J. RTEL1 dismantles T loops and counteracts telomeric G4-DNA to maintain telomere integrity. Cell 149, 795–806 (2012).

25 Broz, P. & Monack, D.M. Newly described pattern recognition receptors team up against intracellular pathogens. Nat. Rev. Immunol. 13, 551–565 (2013).

26 Barber, G.N. Innate immune DNA-sensing pathways: STING, AIMII and the regulation of interferon production and inflammatory responses. Curr. Opin. Immunol. 23, 10–20 (2011).

27 van Steensel, B., Smogorzewska, A. & de Lange, T. TRF2 protects human telomeres from end-to-end fusions. Cell 92, 401–413 (1998).

28 Li, B., Jog, S.P., Reddy, S. & Comai, L. WRN controls formation of extrachromosomal telomeric circles and is required for TRF2DeltaB-mediated telomere shortening. Mol. Cell. Biol. 28, 1892–1904 (2008).

29 Moiseeva, O., Mallette, F.A., Mukhopadhyay, U.K., Moores, A. & Ferbeyre, G. DNA damage signaling and p53-dependent senescence after prolonged beta-interferon stimulation. Mol. Biol. Cell 17, 1583–1592 (2006).

30 Lovejoy, C.A. et al. Loss of ATRX, genome instability, and an altered DNA damage response are hallmarks of the alternative lengthening of telomeres pathway. PLoS Genet. 8, e1002772 (2012).

31 Lewis, P.W., Elsaesser, S.J., Noh, K.M., Stadler, S.C. & Allis, C.D. Daxx is an H3.3-specific histone chaperone and cooperates with ATRX in replication-independent chromatin assembly at telomeres. Proc. Natl. Acad. Sci. USA 107, 14075–14080 (2010).

32 Schwartzentruber, J. et al. Driver mutations in histone H3.3 and chromatin remodeling genes in pediatric glioblastoma. Nature 482, 226–231 (2012).

33 Heaphy, C.M. et al. Altered telomeres in tumors with ATRX and DAXX mutations. Science 333, 425 (2011).

34 Jiao, Y. et al. DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors. Science 331, 1199–1203 (2011).

35 Scherer, M. & Stamminger, T. Emerging role of PML nuclear bodies in innate immune signaling. J. Virol. 90, 5850–5854 (2016).

36 Law, M.J. et al. ATR-X syndrome protein targets tandem repeats and influences allele-specific expression in a size-dependent manner. Cell 143, 367–378 (2010).

37 Wong, L.H. et al. ATRX interacts with H3.3 in maintaining telomere structural integrity in pluripotent embryonic stem cells. Genome Res. 20, 351–360 (2010).

38 Eid, R. et al. Genetic inactivation of ATRX leads to a decrease in the amount of telomeric cohesin and level of telomere transcription in human glioma cells. Mol. Cell. Biol. 35, 2818–2830 (2015).

39 Tchkonia, T., Zhu, Y., van Deursen, J., Campisi, J. & Kirkland, J.L. Cellular senescence and the senescent secretory phenotype: therapeutic opportunities. J. Clin. Invest. 123, 966–972 (2013).

40 Freund, A., Orjalo, A.V., Desprez, P.Y. & Campisi, J. Inflammatory networks during cellular senescence: causes and consequences. Trends Mol. Med. 16, 238–246 (2010).

41 Zitvogel, L., Galluzzi, L., Kepp, O., Smyth, M.J. & Kroemer, G. Type I interferons in anticancer immunity. Nat. Rev. Immunol. 15, 405–414 (2015).

42 Gajewski, T.F. & Corrales, L. New perspectives on type I IFNs in cancer. Cytokine Growth Factor Rev. 26, 175–178 (2015).

43 Woo, S.R., Corrales, L. & Gajewski, T.F. Innate immune recognition of cancer. Annu. Rev. Immunol. 33, 445–474 (2015).

44 Clynes, D. et al. Suppression of the alternative lengthening of telomere pathway by the chromatin remodeling factor ATRX. Nat. Commun. 6, 7538 (2015).

45 Napier, C.E. et al. ATRX represses alternative lengthening of telomeres. Oncotarget 6, 16543–16558 (2015).