Cyclic GMP-AMP synthase recognizes the physical features of DNA.
DNA physical features
STING
cyclic GMP-AMP synthase
cytosolic DNA sensor
innate immune response
Journal
Acta pharmacologica Sinica
ISSN: 1745-7254
Titre abrégé: Acta Pharmacol Sin
Pays: United States
ID NLM: 100956087
Informations de publication
Date de publication:
07 Aug 2024
07 Aug 2024
Historique:
received:
14
05
2024
accepted:
24
07
2024
medline:
8
8
2024
pubmed:
8
8
2024
entrez:
7
8
2024
Statut:
aheadofprint
Résumé
Cyclic GMP-AMP synthase (cGAS) is a major cytosolic DNA sensor that plays a significant role in innate immunity. Upon binding to double stranded DNA (dsDNA), cGAS utilizes GTP and ATP to synthesize the second messenger cyclic GMP-AMP (cGAMP). The cGAMP then binds to the adapter protein stimulator of interferon genes (STING) in the endoplasmic reticulum, resulting in the activation of the transcription factor interferon regulatory factor 3 (IRF3) and subsequent induction of type I interferon. An important question is how cGAS distinguishes between self and non-self DNA. While cGAS binds to the phosphate backbone of DNA without discrimination, its activation is influenced by physical features such as DNA length, inter-DNA distance, and mechanical flexibility. This suggests that the recognition of DNA by cGAS may depend on these physical features. In this article we summarize the recent progress in research on cGAS-STING pathway involved in antiviral defense, cellular senescence and anti-tumor response, and focus on DNA recognition mechanisms based on the physical features.
Identifiants
pubmed: 39112770
doi: 10.1038/s41401-024-01369-7
pii: 10.1038/s41401-024-01369-7
doi:
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.
Références
Brubaker SW, Bonham KS, Zanoni I, Kagan JC. Innate immune pattern recognition: a cell biological perspective. Annu Rev Immunol. 2015;33:257–90.
pubmed: 25581309
pmcid: 5146691
doi: 10.1146/annurev-immunol-032414-112240
Evavold CL, Kagan JC. Inflammasomes: threat-assessment organelles of the innate immune system. Immunity. 2019;51:609–24.
pubmed: 31473100
pmcid: 6801093
doi: 10.1016/j.immuni.2019.08.005
Sun L, Wu J, Du F, Chen X, Chen ZJ. Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science. 2013;339:786–91.
pubmed: 23258413
doi: 10.1126/science.1232458
Li X, Shu C, Yi G, Chaton CT, Shelton CL, Diao J, et al. Cyclic GMP-AMP synthase is activated by double-stranded DNA-induced oligomerization. Immunity. 2013;39:1019–31.
pubmed: 24332030
doi: 10.1016/j.immuni.2013.10.019
Wu J, Sun L, Chen X, Du F, Shi H, Chen C, et al. Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA. Science. 2013;339:826–30.
pubmed: 23258412
doi: 10.1126/science.1229963
Zhang C, Shang G, Gui X, Zhang X, Bai XC, Chen ZJ. Structural basis of STING binding with and phosphorylation by TBK1. Nature. 2019;567:394–8.
pubmed: 30842653
pmcid: 6862768
doi: 10.1038/s41586-019-1000-2
Liu S, Cai X, Wu J, Cong Q, Chen X, Li T, et al. Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation. Science. 2015;347:aaa2630.
pubmed: 25636800
doi: 10.1126/science.aaa2630
Wu X, Wu FH, Wang X, Wang L, Siedow JN, Zhang W, et al. Molecular evolutionary and structural analysis of the cytosolic DNA sensor cGAS and STING. Nucleic Acids Res. 2014;42:8243–57.
pubmed: 24981511
pmcid: 4117786
doi: 10.1093/nar/gku569
Martin M, Hiroyasu A, Guzman RM, Roberts SA, Goodman AG. Analysis of Drosophila STING reveals an evolutionarily conserved antimicrobial function. Cell Rep. 2018;23:3537–50.e6.
pubmed: 29924997
pmcid: 6114933
doi: 10.1016/j.celrep.2018.05.029
Si W, Liang H, Bugno J, Xu Q, Ding X, Yang K, et al. Lactobacillus rhamnosus GG induces cGAS/STING- dependent type I interferon and improves response to immune checkpoint blockade. Gut. 2022;71:521–33.
pubmed: 33685966
doi: 10.1136/gutjnl-2020-323426
Lv M, Chen M, Zhang R, Zhang W, Wang C, Zhang Y, et al. Manganese is critical for antitumor immune responses via cGAS-STING and improves the efficacy of clinical immunotherapy. Cell Res. 2020;30:966–79.
pubmed: 32839553
pmcid: 7785004
doi: 10.1038/s41422-020-00395-4
Luo WW, Tong Z, Cao P, Wang FB, Liu Y, Zheng ZQ, et al. Transcription-independent regulation of STING activation and innate immune responses by IRF8 in monocytes. Nat Commun. 2022;13:4822.
pubmed: 35973990
pmcid: 9381507
doi: 10.1038/s41467-022-32401-1
Zeng PH, Yin WJ. The cGAS/STING signaling pathway: a cross-talk of infection, senescence and tumors. Cell Cycle. 2023;22:38–56.
pubmed: 35946607
doi: 10.1080/15384101.2022.2109899
Gluck S, Guey B, Gulen MF, Wolter K, Kang TW, Schmacke NA, et al. Innate immune sensing of cytosolic chromatin fragments through cGAS promotes senescence. Nat Cell Biol. 2017;19:1061–70.
pubmed: 28759028
pmcid: 5826565
doi: 10.1038/ncb3586
Xia PY, Wang S, Gao P, Gao GX, Fan ZS. DNA sensor cGAS-mediated immune recognition. Protein Cell. 2016;7:777–91.
pubmed: 27696330
pmcid: 5084157
doi: 10.1007/s13238-016-0320-3
Wu JX, Chen ZJ. Innate immune sensing and signaling of cytosolic nucleic acids. Annu Rev Immunol. 2014;32:461–88.
pubmed: 24655297
doi: 10.1146/annurev-immunol-032713-120156
Cao DJ, Schiattarella GG, Villalobos E, Jiang N, May HI, Li T, et al. Cytosolic DNA sensing promotes macrophage transformation and governs myocardial ischemic injury. Circulation. 2018;137:2613–34.
pubmed: 29437120
pmcid: 5997506
doi: 10.1161/CIRCULATIONAHA.117.031046
Ablasser A, Chen ZJJ. cGAS in action: Expanding roles in immunity and inflammation. Science. 2019;363:1055.
doi: 10.1126/science.aat8657
Su S, Hua D, Li JP, Zhang XN, Bai L, Cao LB, et al. Modulation of innate immune response to viruses including SARS-CoV-2 by progesterone. Signal Transduct Target Ther. 2022;7:137.
pubmed: 35468896
pmcid: 9035769
doi: 10.1038/s41392-022-00981-5
Volkman HE, Cambier S, Gray EE, Stetson DB. Tight nuclear tethering of cGAS is essential for preventing autoreactivity. Elife. 2019;8:e47491.
pubmed: 31808743
pmcid: 6927687
doi: 10.7554/eLife.47491
Gentili M, Lahaye X, Nadalin F, Nader GPF, Puig Lombardi E, Herve S, et al. The N-terminal domain of cGAS determines preferential association with centromeric DNA and innate immune activation in the nucleus. Cell Rep. 2019;26:2377–93.e13.
pubmed: 30811988
pmcid: 6391843
doi: 10.1016/j.celrep.2019.01.105
Barnett KC, Coronas-Serna JM, Zhou W, Ernandes MJ, Cao A, Kranzusch PJ, et al. Phosphoinositide interactions position cGAS at the plasma membrane to ensure efficient distinction between self- and viral DNA. Cell. 2019;176:1432–46.e11.
pubmed: 30827685
pmcid: 6697112
doi: 10.1016/j.cell.2019.01.049
Qiu S, Zhong X, Meng X, Li S, Qian X, Lu H, et al. Mitochondria-localized cGAS suppresses ferroptosis to promote cancer progression. Cell Res. 2023;33:299–311.
pubmed: 36864172
pmcid: 10066369
doi: 10.1038/s41422-023-00788-1
Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell. 2006;124:783–801.
pubmed: 16497588
doi: 10.1016/j.cell.2006.02.015
Civril F, Deimling T, de Oliveira Mann CC, Ablasser A, Moldt M, Witte G, et al. Structural mechanism of cytosolic DNA sensing by cGAS. Nature. 2013;498:332–7.
pubmed: 23722159
pmcid: 3768140
doi: 10.1038/nature12305
Decout A, Katz JD, Venkatraman S, Ablasser A. The cGAS-STING pathway as a therapeutic target in inflammatory diseases. Nat Rev Immunol. 2021;21:548–69.
pubmed: 33833439
pmcid: 8029610
doi: 10.1038/s41577-021-00524-z
Shi X, Wang S, Wu Y, Li Q, Zhang T, Min K, et al. A bibliometric analysis of the innate immune DNA sensing cGAS-STING pathway from 2013 to 2021. Front Immunol. 2022;13:916383.
pubmed: 35720348
pmcid: 9204223
doi: 10.3389/fimmu.2022.916383
Dobbs N, Burnaevskiy N, Chen D, Gonugunta VK, Alto NM, Yan N. STING activation by translocation from the ER is associated with infection and autoinflammatory disease. Cell Host Microbe. 2015;18:157–68.
pubmed: 26235147
pmcid: 4537353
doi: 10.1016/j.chom.2015.07.001
Diamond MS, Kinder M, Matsushita H, Mashayekhi M, Dunn GP, Archambault JM, et al. Type I interferon is selectively required by dendritic cells for immune rejection of tumors. J Exp Med. 2011;208:1989–2003.
pubmed: 21930769
pmcid: 3182061
doi: 10.1084/jem.20101158
Nicolai CJ, Wolf N, Chang IC, Kirn G, Marcus A, Ndubaku CO, et al. NK cells mediate clearance of CD8
pubmed: 32198222
pmcid: 7228660
doi: 10.1126/sciimmunol.aaz2738
Ishikawa H, Barber GN. STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling. Nature. 2008;455:674–8.
pubmed: 18724357
pmcid: 2804933
doi: 10.1038/nature07317
Gonugunta VK, Sakai T, Pokatayev V, Yang K, Wu J, Dobbs N, et al. Trafficking-mediated STING degradation requires sorting to acidified endolysosomes and can be targeted to enhance anti-tumor response. Cell Rep. 2017;21:3234–42.
pubmed: 29241549
pmcid: 5905341
doi: 10.1016/j.celrep.2017.11.061
Luo W, Wang Y, Zhang L, Ren P, Zhang C, Li Y, et al. Critical role of cytosolic DNA and its sensing adaptor STING in aortic degeneration, dissection, and rupture. Circulation. 2020;141:42–66.
pubmed: 31887080
doi: 10.1161/CIRCULATIONAHA.119.041460
Wang X, Majumdar T, Kessler P, Ozhegov E, Zhang Y, Chattopadhyay S, et al. STING requires the adaptor TRIF to trigger innate immune responses to microbial infection. Cell Host Microbe. 2016;20:329–41.
pubmed: 27631700
pmcid: 5026396
doi: 10.1016/j.chom.2016.08.002
Ma Z, Jacobs SR, West JA, Stopford C, Zhang Z, Davis Z, et al. Modulation of the cGAS-STING DNA sensing pathway by gammaherpesviruses. Proc Natl Acad Sci USA. 2015;112:E4306–E15.
pubmed: 26199418
pmcid: 4534226
doi: 10.1073/pnas.1503831112
Skouboe MK, Knudsen A, Reinert LS, Boularan C, Lioux T, Perouzel E, et al. STING agonists enable antiviral cross-talk between human cells and confer protection against genital herpes in mice. PLoS Pathog. 2018;14:e1006976.
pubmed: 29608601
pmcid: 5897032
doi: 10.1371/journal.ppat.1006976
Gao D, Wu J, Wu YT, Du F, Aroh C, Yan N, et al. Cyclic GMP-AMP synthase is an innate immune sensor of HIV and other retroviruses. Science. 2013;341:903–6.
pubmed: 23929945
doi: 10.1126/science.1240933
Lima-Junior DS, Krishnamurthy SR, Bouladoux N, Collins N, Han SJ, Chen EY, et al. Endogenous retroviruses promote homeostatic and inflammatory responses to the microbiota. Cell. 2021;184:3794–811.e19.
pubmed: 34166614
pmcid: 8381240
doi: 10.1016/j.cell.2021.05.020
Canadas I, Thummalapalli R, Kim JW, Kitajima S, Jenkins RW, Christensen CL, et al. Tumor innate immunity primed by specific interferon-stimulated endogenous retroviruses. Nat Med. 2018;24:1143–50.
pubmed: 30038220
pmcid: 6082722
doi: 10.1038/s41591-018-0116-5
Eaglesham JB, Pan Y, Kupper TS, Kranzusch PJ. Viral and metazoan poxins are cGAMP-specific nucleases that restrict cGAS-STING signalling. Nature. 2019;566:259–63.
pubmed: 30728498
pmcid: 6640140
doi: 10.1038/s41586-019-0928-6
Ma Z, Damania B. The cGAS-STING defense pathway and its counteraction by viruses. Cell Host Microbe. 2016;19:150–8.
pubmed: 26867174
pmcid: 4755325
doi: 10.1016/j.chom.2016.01.010
Lau L, Gray EE, Brunette RL, Stetson DB. DNA tumor virus oncogenes antagonize the cGAS-STING DNA-sensing pathway. Science. 2015;350:568–71.
pubmed: 26405230
doi: 10.1126/science.aab3291
Dougan M, Dranoff G. Immune therapy for cancer. Annu Rev Immunol. 2009;27:83–117.
pubmed: 19007331
doi: 10.1146/annurev.immunol.021908.132544
Wu SY, Xiao Y, Wei JL, Xu XE, Jin X, Hu X, et al. MYC suppresses STING-dependent innate immunity by transcriptionally upregulating DNMT1 in triple-negative breast cancer. J Immunother Cancer. 2021;9:e002528.
pubmed: 34321275
pmcid: 8320259
doi: 10.1136/jitc-2021-002528
Woo SR, Fuertes MB, Corrales L, Spranger S, Furdyna MJ, Leung MY, et al. STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors. Immunity. 2014;41:830–42.
pubmed: 25517615
pmcid: 4384884
doi: 10.1016/j.immuni.2014.10.017
Corrales L, Glickman LH, McWhirter SM, Kanne DB, Sivick KE, Katibah GE, et al. Direct activation of STING in the tumor microenvironment leads to potent and systemic tumor regression and immunity. Cell Rep. 2015;11:1018–30.
pubmed: 25959818
pmcid: 4440852
doi: 10.1016/j.celrep.2015.04.031
Crasta K, Ganem NJ, Dagher R, Lantermann AB, Ivanova EV, Pan Y, et al. DNA breaks and chromosome pulverization from errors in mitosis. Nature. 2012;482:53–8.
pubmed: 22258507
pmcid: 3271137
doi: 10.1038/nature10802
Harding SM, Benci JL, Irianto J, Discher DE, Minn AJ, Greenberg RA. Mitotic progression following DNA damage enables pattern recognition within micronuclei. Nature. 2017;548:466–70.
pubmed: 28759889
pmcid: 5857357
doi: 10.1038/nature23470
Mackenzie KJ, Carroll P, Martin CA, Murina O, Fluteau A, Simpson DJ, et al. cGAS surveillance of micronuclei links genome instability to innate immunity. Nature. 2017;548:461–5.
pubmed: 28738408
pmcid: 5870830
doi: 10.1038/nature23449
Ahn J, Konno H, Barber GN. Diverse roles of STING-dependent signaling on the development of cancer. Oncogene. 2015;34:5302–8.
pubmed: 25639870
pmcid: 4998969
doi: 10.1038/onc.2014.457
Xiaohong L, Zhenting Z, Yunjie Y, Wei C, Xiangjin X, Kun X, et al. Activation of the STING-IRF3 pathway involved in psoriasis with diabetes mellitus. J Cell Mol Med. 2022;26:2139–51.
pubmed: 35174638
pmcid: 8995451
doi: 10.1111/jcmm.17236
Seo J, Kim H, Min KI, Kim C, Kwon Y, Zheng Z, et al. Weight-bearing activity impairs nuclear membrane and genome integrity via YAP activation in plantar melanoma. Nat Commun. 2022;13:2214.
pubmed: 35468978
pmcid: 9038926
doi: 10.1038/s41467-022-29925-x
Guo E, Xiao R, Wu Y, Lu F, Liu C, Yang B, et al. WEE1 inhibition induces anti-tumor immunity by activating ERV and the dsRNA pathway. J Exp Med. 2022;219:e20210789.
pubmed: 34825915
doi: 10.1084/jem.20210789
Chen H, Chen H, Zhang J, Wang Y, Simoneau A, Yang H, et al. cGAS suppresses genomic instability as a decelerator of replication forks. Sci Adv. 2020;6:eabb8941.
pubmed: 33055160
pmcid: 7556829
doi: 10.1126/sciadv.abb8941
Suter MA, Tan NY, Thiam CH, Khatoo M, MacAry PA, Angeli V, et al. cGAS-STING cytosolic DNA sensing pathway is suppressed by JAK2-STAT3 in tumor cells. Sci Rep. 2021;11:7243.
pubmed: 33790360
pmcid: 8012641
doi: 10.1038/s41598-021-86644-x
Huang KC, Chiang SF, Chang HY, Chen WT, Yang PC, Chen TW, et al. Engineered sTRAIL-armed MSCs overcome STING deficiency to enhance the therapeutic efficacy of radiotherapy for immune checkpoint blockade. Cell Death Dis. 2022;13:610.
pubmed: 35835756
pmcid: 9283452
doi: 10.1038/s41419-022-05069-0
Konno H, Yamauchi S, Berglund A, Putney RM, Mule JJ, Barber GN. Suppression of STING signaling through epigenetic silencing and missense mutation impedes DNA damage mediated cytokine production. Oncogene. 2018;37:2037–51.
pubmed: 29367762
pmcid: 6029885
doi: 10.1038/s41388-017-0120-0
Yang Y, Wu M, Cao D, Yang C, Jin J, Wu L, et al. ZBP1-MLKL necroptotic signaling potentiates radiation-induced antitumor immunity via intratumoral STING pathway activation. Sci Adv. 2021;7:eabf6290.
pubmed: 34613770
pmcid: 8494295
doi: 10.1126/sciadv.abf6290
Demaria O, De Gassart A, Coso S, Gestermann N, Di Domizio J, Flatz L, et al. STING activation of tumor endothelial cells initiates spontaneous and therapeutic antitumor immunity. Proc Natl Acad Sci USA. 2015;112:15408–13.
pubmed: 26607445
pmcid: 4687570
doi: 10.1073/pnas.1512832112
Nagata M, Kosaka A, Yajima Y, Yasuda S, Ohara M, Ohara K, et al. A critical role of STING-triggered tumor-migrating neutrophils for anti-tumor effect of intratumoral cGAMP treatment. Cancer Immunol Immunother. 2021;70:2301–12.
pubmed: 33507344
pmcid: 10992389
doi: 10.1007/s00262-021-02864-0
Messaoud-Nacer Y, Culerier E, Rose S, Maillet I, Rouxel N, Briault S, et al. STING agonist diABZI induces PANoptosis and DNA mediated acute respiratory distress syndrome (ARDS). Cell Death Dis. 2022;13:269.
pubmed: 35338116
pmcid: 8953969
doi: 10.1038/s41419-022-04664-5
Motedayen Aval L, Pease JE, Sharma R, Pinato DJ. Challenges and opportunities in the clinical development of STING agonists for cancer immunotherapy. J Clin Med. 2020;9:3323.
pubmed: 33081170
pmcid: 7602874
doi: 10.3390/jcm9103323
Le Naour J, Zitvogel L, Galluzzi L, Vacchelli E, Kroemer G. Trial watch: STING agonists in cancer therapy. Oncoimmunology. 2020;9:1777624.
pubmed: 32934881
pmcid: 7466854
doi: 10.1080/2162402X.2020.1777624
Lemos H, Mohamed E, Huang L, Ou R, Pacholczyk G, Arbab AS, et al. STING promotes the growth of tumors characterized by low antigenicity via IDO activation. Cancer Res. 2016;76:2076–81.
pubmed: 26964621
pmcid: 4873329
doi: 10.1158/0008-5472.CAN-15-1456
Li S, Mirlekar B, Johnson BM, Brickey WJ, Wrobel JA, Yang N, et al. STING-induced regulatory B cells compromise NK function in cancer immunity. Nature. 2022;610:373–80.
pubmed: 36198789
pmcid: 9875944
doi: 10.1038/s41586-022-05254-3
Gorgoulis V, Adams PD, Alimonti A, Bennett DC, Bischof O, Bishop C, et al. Cellular senescence: defining a path forward. Cell. 2019;179:813–27.
pubmed: 31675495
doi: 10.1016/j.cell.2019.10.005
Dou Z, Ghosh K, Vizioli MG, Zhu J, Sen P, Wangensteen KJ, et al. Cytoplasmic chromatin triggers inflammation in senescence and cancer. Nature. 2017;550:402–6.
pubmed: 28976970
pmcid: 5850938
doi: 10.1038/nature24050
Takahashi A, Loo TM, Okada R, Kamachi F, Watanabe Y, Wakita M, et al. Downregulation of cytoplasmic DNases is implicated in cytoplasmic DNA accumulation and SASP in senescent cells. Nat Commun. 2018;9:1249.
pubmed: 29593264
pmcid: 5871854
doi: 10.1038/s41467-018-03555-8
Zhong L, Hu MM, Bian LJ, Liu Y, Chen Q, Shu HB. Phosphorylation of cGAS by CDK1 impairs self-DNA sensing in mitosis. Cell Discov. 2020;6:26.
pubmed: 32351706
pmcid: 7186227
doi: 10.1038/s41421-020-0162-2
Zhao B, Xu P, Rowlett CM, Jing T, Shinde O, Lei Y, et al. The molecular basis of tight nuclear tethering and inactivation of cGAS. Nature. 2020;587:673–7.
pubmed: 32911481
pmcid: 7704945
doi: 10.1038/s41586-020-2749-z
Cao D, Han X, Fan X, Xu RM, Zhang X. Structural basis for nucleosome-mediated inhibition of cGAS activity. Cell Res. 2020;30:1088–97.
pubmed: 33051594
pmcid: 7784699
doi: 10.1038/s41422-020-00422-4
Pathare GR, Decout A, Gluck S, Cavadini S, Makasheva K, Hovius R, et al. Structural mechanism of cGAS inhibition by the nucleosome. Nature. 2020;587:668–72.
pubmed: 32911482
doi: 10.1038/s41586-020-2750-6
Dharan A, Bachmann N, Talley S, Zwikelmaier V, Campbell EM. Nuclear pore blockade reveals that HIV-1 completes reverse transcription and uncoating in the nucleus. Nat Microbiol. 2020;5:1088–95.
pubmed: 32483230
pmcid: 9286700
doi: 10.1038/s41564-020-0735-8
Li CL, Burdick RC, Nagashima K, Hu WS, Pathak VK. HIV-1 cores retain their integrity until minutes before uncoating in the nucleus. Proc Natl Acad Sci USA. 2021;118:e2019467118.
pubmed: 33649225
pmcid: 7958386
doi: 10.1073/pnas.2019467118
Zila V, Margiotta E, Turonova B, Muller TG, Zimmerli CE, Mattei S, et al. Cone-shaped HIV-1 capsids are transported through intact nuclear pores. Cell. 2021;184:1032–46.e18.
pubmed: 33571428
pmcid: 7895898
doi: 10.1016/j.cell.2021.01.025
Li T, Huang T, Du M, Chen X, Du F, Ren J, et al. Phosphorylation and chromatin tethering prevent cGAS activation during mitosis. Science. 2021;371:eabc5386.
pubmed: 33542149
pmcid: 8171060
doi: 10.1126/science.abc5386
Sun H, Huang Y, Mei S, Xu FW, Liu XM, Zhao F, et al. A nuclear export signal is required for cGAS to sense cytosolic DNA. Cell Rep. 2021;34:108586.
pubmed: 33406424
doi: 10.1016/j.celrep.2020.108586
Lahaye X, Gentili M, Silvin A, Conrad C, Picard L, Jouve M, et al. NONO detects the nuclear HIV capsid to promote cGAS-mediated innate immune activation. Cell. 2018;175:488–501.e22.
pubmed: 30270045
doi: 10.1016/j.cell.2018.08.062
Wu YK, Song K, Hao WZ, Li J, Wang LY, Li ST. Nuclear soluble cGAS senses double-stranded DNA virus infection. Commun Biol. 2022;5:433.
pubmed: 35538147
pmcid: 9090744
doi: 10.1038/s42003-022-03400-1
Roos WH, Ivanovska IL, Evilevitch A, Wuite GJ. Viral capsids: mechanical characteristics, genome packaging and delivery mechanisms. Cell Mol Life Sci. 2007;64:1484–97.
pubmed: 17440680
pmcid: 2771126
doi: 10.1007/s00018-007-6451-1
Gong L, Ou X, Hu L, Zhong J, Li J, Deng S, et al. The molecular mechanism of Herpes Simplex Virus 1 UL31 in antagonizing the activity of IFN-beta. Microbiol Spectr. 2022;10:e0188321.
pubmed: 35196784
doi: 10.1128/spectrum.01883-21
Sun X, Fu P, Xie L, Chai S, Xu Q, Zeng L, et al. Resveratrol inhibits the progression of cervical cancer by suppressing the transcription and expression of HPV E6 and E7 genes. Int J Mol Med. 2021;47:335–45.
pubmed: 33236130
doi: 10.3892/ijmm.2020.4789
Bauer DW, Huffman JB, Homa FL, Evilevitch A. Herpes virus genome, the pressure is on. J Am Chem Soc. 2013;135:11216–21.
pubmed: 23829592
pmcid: 4019375
doi: 10.1021/ja404008r
Smith DE, Tans SJ, Smith SB, Grimes S, Anderson DL, Bustamante C. The bacteriophage straight phi29 portal motor can package DNA against a large internal force. Nature. 2001;413:748–52.
pubmed: 11607035
doi: 10.1038/35099581
Jiang W, Chang J, Jakana J, Weigele P, King J, Chiu W. Structure of epsilon15 bacteriophage reveals genome organization and DNA packaging/injection apparatus. Nature. 2006;439:612–6.
pubmed: 16452981
pmcid: 1559657
doi: 10.1038/nature04487
Liu YT, Jih J, Dai X, Bi GQ, Zhou ZH. Cryo-EM structures of herpes simplex virus type 1 portal vertex and packaged genome. Nature. 2019;570:257–61.
pubmed: 31142842
pmcid: 6732574
doi: 10.1038/s41586-019-1248-6
Wang F, Zhou Y, Cheng S, Lou J, Zhang X, He Q, et al. Gint4.T-modified DNA tetrahedrons loaded with doxorubicin inhibits glioma cell proliferation by targeting PDGFRbeta. Nanoscale Res Lett. 2020;15:150.
pubmed: 32691170
pmcid: 7371771
doi: 10.1186/s11671-020-03377-y
Abad-Valle P, Fernandez-Abedul MT, Costa-Garcia A. DNA single-base mismatch study with an electrochemical enzymatic genosensor. Biosens Bioelectron. 2007;22:1642–50.
pubmed: 16950611
doi: 10.1016/j.bios.2006.07.015
Firpo MR, Mounce BC. Diverse functions of polyamines in virus infection. Biomolecules. 2020;10:628.
pubmed: 32325677
pmcid: 7226272
doi: 10.3390/biom10040628
Gibson W, Roizman B. Compartmentalization of spermine and spermidine in the herpes simplex virion. Proc Natl Acad Sci USA. 1971;68:2818–21.
pubmed: 5288261
pmcid: 389533
doi: 10.1073/pnas.68.11.2818
Ames BN, Dubin DT. The role of polyamines in the neutralization of bacteriophage deoxyribonucleic acid. J Biol Chem. 1960;235:769–75.
pubmed: 13793161
doi: 10.1016/S0021-9258(19)67936-6
Flink I, Pettijohn DE. Polyamines stabilise DNA folds. Nature. 1975;253:62–3.
pubmed: 1110753
doi: 10.1038/253062a0
Pelta J, Livolant F, Sikorav JL. DNA aggregation induced by polyamines and cobalthexamine. J Biol Chem. 1996;271:5656–62.
pubmed: 8621429
doi: 10.1074/jbc.271.10.5656
Bauer DW, Li D, Huffman J, Homa FL, Wilson K, Leavitt JC, et al. Exploring the balance between DNA pressure and capsid stability in herpesviruses and phages. J Virol. 2015;89:9288–98.
pubmed: 26136570
pmcid: 4542358
doi: 10.1128/JVI.01172-15
Sun J, Liu C, Peng R, Zhang FK, Tong Z, Liu S, et al. Cryo-EM structure of the varicella-zoster virus A-capsid. Nat Commun. 2020;11:4795.
pubmed: 32963252
pmcid: 7508878
doi: 10.1038/s41467-020-18537-y
Zhou S, Fu Z, Zhang Z, Jia X, Xu G, Sun L, et al. Liquid-liquid phase separation mediates the formation of herpesvirus assembly compartments. J Cell Biol. 2023;222:e202201088.
pubmed: 36250941
doi: 10.1083/jcb.202201088
Xu JX, Jiang X, Zhang YL, Dong Y, Ma CL, Jiang HQ, et al. Multiscale characterization reveals oligomerization dependent phase separation of primer-independent RNA polymerase nsp8 from SARS-CoV-2. Commun Biol. 2022;5:925.
pubmed: 36071105
pmcid: 9451113
doi: 10.1038/s42003-022-03892-x
Wang L, Li S, Wang K, Wang N, Liu Q, Sun Z, et al. Spermine enhances antiviral and anticancer responses by stabilizing DNA binding with the DNA sensor cGAS. Immunity. 2023;56:272–88.e7.
pubmed: 36724787
doi: 10.1016/j.immuni.2023.01.001
Wang L, Li S, Wang K, Wang N, Liu Q, Sun Z, et al. DNA mechanical flexibility controls DNA potential to activate cGAS-mediated immune surveillance. Nat Commun. 2022;13:7107.
pubmed: 36402783
pmcid: 9675814
doi: 10.1038/s41467-022-34858-6
Basu A, Bobrovnikov DG, Ha T. DNA mechanics and its biological impact. J Mol Biol. 2021;433:166861.
pubmed: 33539885
doi: 10.1016/j.jmb.2021.166861
Furukawa A, Walinda E, Arita K, Sugase K. Structural dynamics of double-stranded DNA with epigenome modification. Nucleic Acids Res. 2021;49:1152–62.
pubmed: 33337470
doi: 10.1093/nar/gkaa1210
Saran R, Wang Y, Li ITS. Mechanical flexibility of DNA: a quintessential tool for DNA nanotechnology. Sens. 2020;20:7019.
doi: 10.3390/s20247019
Basu A, Bobrovnikov DG, Qureshi Z, Kayikcioglu T, Ngo TTM, Ranjan A, et al. Measuring DNA mechanics on the genome scale. Nature. 2021;589:462.
pubmed: 33328628
doi: 10.1038/s41586-020-03052-3
Song CL, Wang LN, Wu XY, Wang K, Xie D, Xiao Q, et al. PML Recruits TET2 to regulate DNA modification and cell proliferation in response to chemotherapeutic agent. Cancer Res. 2018;78:2475–89.
pubmed: 29735542
pmcid: 6386530
doi: 10.1158/0008-5472.CAN-17-3091
Luecke S, Holleufer A, Christensen MH, Jonsson KL, Boni GA, Sorensen LK, et al. cGAS is activated by DNA in a length-dependent manner. Embo Rep. 2017;18:1707–15.
pubmed: 28801534
pmcid: 5623850
doi: 10.15252/embr.201744017
Andreeva L, Hiller B, Kostrewa D, Lassig C, de Oliveira Mann CC, Jan Drexler D, et al. cGAS senses long and HMGB/TFAM-bound U-turn DNA by forming protein-DNA ladders. Nature. 2017;549:394–8.
pubmed: 28902841
doi: 10.1038/nature23890
Zhou W, Whiteley AT, Mann CCD, Morehouse BR, Nowak RP, Fischer ES, et al. Structure of the human cGAS-DNA complex reveals enhanced control of immune surveillance. Cell. 2018;174:300.
pubmed: 30007416
pmcid: 6084792
doi: 10.1016/j.cell.2018.06.026
Du M, Chen ZJ. DNA-induced liquid phase condensation of cGAS activates innate immune signaling. Science. 2018;361:704–9.
pubmed: 29976794
pmcid: 9417938
doi: 10.1126/science.aat1022
Xie W, Lama L, Adura C, Tomita D, Glickman JF, Tuschl T, et al. Human cGAS catalytic domain has an additional DNA-binding interface that enhances enzymatic activity and liquid-phase condensation. Proc Natl Acad Sci USA. 2019;116:11946–55.
pubmed: 31142647
pmcid: 6575157
doi: 10.1073/pnas.1905013116
Gavin AL, Huang D, Huber C, Martensson A, Tardif V, Skog PD, et al. PLD3 and PLD4 are single-stranded acid exonucleases that regulate endosomal nucleic-acid sensing. Nat Immunol. 2018;19:942–53.
pubmed: 30111894
pmcid: 6105523
doi: 10.1038/s41590-018-0179-y
Rigby RE, Leitch A, Jackson AP. Nucleic acid-mediated inflammatory diseases. Bioessays. 2008;30:833–42.
pubmed: 18693262
doi: 10.1002/bies.20808
Morita M, Stamp G, Robins P, Dulic A, Rosewell I, Hrivnak G, et al. Gene-targeted mice lacking the Trex1 (DNase III) 3’–>5’ DNA exonuclease develop inflammatory myocarditis. Mol Cell Biol. 2004;24:6719–27.
pubmed: 15254239
pmcid: 444847
doi: 10.1128/MCB.24.15.6719-6727.2004
Gao DX, Li T, Li XD, Chen X, Li QZ, Wight-Carter M, et al. Activation of cyclic GMP-AMP synthase by self-DNA causes autoimmune diseases. Proc Natl Acad Sci USA. 2015;112:E5699–E705.
pubmed: 26371324
pmcid: 4620884
doi: 10.1073/pnas.1516465112
Zhao M, Xia T, Xing JQ, Yin LH, Li XW, Pan J, et al. The stress granule protein G3BP1 promotes pre-condensation of cGAS to allow rapid responses to DNA. Embo Rep. 2022;23:e53166.
pubmed: 34779554
doi: 10.15252/embr.202153166
Wang LN, Liu QL, Wang N, Li SR, Bian W, Sun Z, et al. Oleic acid dissolves cGAS-DNA phase separation to inhibit immune surveillance. Adv Sci. 2023;10:e2206820.
doi: 10.1002/advs.202206820
Xu G, Liu C, Zhou S, Li Q, Feng Y, Sun P, et al. Viral tegument proteins restrict cGAS-DNA phase separation to mediate immune evasion. Mol Cell. 2021;81:2823–37.e9.
pubmed: 34015248
doi: 10.1016/j.molcel.2021.05.002
Ghosh M, Saha S, Li J, Montrose DC, Martinez LA. p53 engages the cGAS/STING cytosolic DNA sensing pathway for tumor suppression. Mol Cell. 2023;83:266–80.e6.
pubmed: 36638783
pmcid: 9993620
doi: 10.1016/j.molcel.2022.12.023
Liu H, Yan Z, Zhu D, Xu H, Liu F, Chen T, et al. CD-NTase family member MB21D2 promotes cGAS-mediated antiviral and antitumor immunity. Cell Death Differ. 2023;30:992–1004.
pubmed: 36681781
pmcid: 9864494
doi: 10.1038/s41418-023-01116-1
Morrone SR, Wang T, Constantoulakis LM, Hooy RM, Delannoy MJ, Sohn J. Cooperative assembly of IFI16 filaments on dsDNA provides insights into host defense strategy. Proc Natl Acad Sci USA. 2014;111:E62–71.
pubmed: 24367117
doi: 10.1073/pnas.1313577111