IMMUNOLOGY DNA-induced liquid phase …...IMMUNOLOGY DNA-induced liquid phase condensation of cGAS activates innate immune signaling Mingjian Du1,2 and Zhijian J. Chen1,2,3* The binding

IMMUNOLOGY

DNA-induced liquid phasecondensation of cGAS activatesinnate immune signalingMingjian Du1,2 and Zhijian J. Chen1,2,3*

The binding of DNA to cyclic GMP–AMP synthase (cGAS) leads to the production of thesecondary messenger cyclic GMP–AMP (cGAMP), which activates innate immuneresponses. We have shown that DNA binding to cGAS robustly induced the formation ofliquidlike droplets in which cGAS was activated. The disordered and positively chargedcGAS N terminus enhanced cGAS-DNA phase separation by increasing the valenciesof DNA binding. Long DNA was more efficient in promoting cGAS liquid phase separationand cGAS enzyme activity than short DNA. Moreover, free zinc ions enhanced cGASenzyme activity both in vitro and in cells by promoting cGAS-DNA phase separation. Theseresults demonstrated that the DNA-induced phase transition of cGAS promotes cGAMPproduction and innate immune signaling.

Cyclic GMP–AMP synthase (cGAS) is aDNA-sensing enzyme that catalyzes the conver-sion of GTP and ATP to cyclic GMP–AMP(cGAMP), which activates the adaptorprotein STING (1, 2). This, in turn, induces

type I interferons and other cytokines (3–5). DNAarising in the cytoplasmactivates cGAS and drivesthe formation of cytoplasmic foci containing cGASand DNA (1). However, the molecular mechanismand functional effect of such cGAS foci are poorlyunderstood. cGAS contains a disordered andpositively charged N terminus and a structuredC terminus harboring a nucleotidyltransferasedomain (core cGAS). Both the N and C terminiof cGAS bind to DNA irrespective of DNA se-quence (6–11). We hypothesized that such multi-valent interactions could lead to the formationof largemembraneless protein foci through liquidphase separation (Fig. 1A). This physicochemicalprocess has emerged as a keymechanism under-lying the formation of cellular bodies such as Pgranules and nucleoli (12–20).To test whether DNA binding induces phase

separation of cGAS in vitro, we incubated fluo-rescently labeled cGAS protein (fig. S1A) withdouble-stranded DNA (dsDNA) oligonucleotides[100 base pairs (bp)] (table S1 andmethods). Uponmixing, cGAS and DNA formed micrometer-sizedliquid droplets within 2 min (Fig. 1B and movieS1). Small liquid droplets fused into larger ones(Fig. 1C), accompanied by increased fluorescenceintensity and larger equivalent diameter (Fig. 1,D and E, and movie S1). Fluorescence recoveryafter photobleaching (FRAP) experiments showedthat when bleaching was performed 30 min after

the initiation of phase separation, the fluores-cence of cGAS or DNAwas efficiently recoveredin a temperature-dependentmanner (Fig. 1F andfig. S1, B to D). In contrast, when bleaching oc-curred 2 hours after mixing of cGAS and DNA,the fluorescence recovery was much slower (Fig.1F and fig. S1D). Thus, cGAS and DNAmoleculeswithin the liquid droplets are mobile and exhibitdynamic internal rearrangement in the early phasebut gradually undergo a liquid-to-solid transitionand mature into a gel-like state (Fig. 1F) (19, 21).cGAS and DNA formed liquid droplets when

the concentration of each exceeded 30 nM (Fig.1G) in a buffer mimicking physiological ion con-centrations and the composition of the cytoplasm(physiological buffer) (methods). Measurementsof cGAMP production by cGAS revealed thatthe specific activity of cGAS substantially in-creased at concentrations above 30 nM (Fig. 1Hand methods). The in vitro cGAS-DNA phasetransitionwasweakened by increasing salt (NaCl)concentrations (fig. S2A), suggesting that ionicinteractions between cGAS and DNA were im-portant for the phase transition. A 45-bp dsDNAcommonly used for the stimulation of the cGASpathway [immune stimulatory DNA (ISD)] alsorobustly induced cGAS liquid droplet formation(fig. S2, B to D). This effect was abolished bytreatment with Benzonase, which degrades DNA(fig. S2E). cGAS also formed liquid droplets with45-bp double-stranded RNA (fig. S2F), but RNAdid not activate cGAS to produce cGAMP (fig.S2G). These results are consistent with previousstructural studies indicating that DNA but notRNA binding induces a conformational changethat activates cGAS (7). Thus, liquid phase separa-tion is insufficient for cGAS activation in theabsence of the correct conformational changeinduced by DNA.The cGAS-DNA phase separation was unaf-

fected by the addition of ATP, GTP, or a com-bination thereof (fig. S3A). Moreover, ATP orGTP could be partitioned into and enriched in

the cGAS-DNA liquid droplets (fig. S3, B and C).FRAP experiments showed that ATP was rapidlyexchanged into andout of the cGAS-DNAdroplets(fig. S3D).We next examined the formation of cGAS-

DNA foci within cells. In the human fibroblastcell line BJ-5ta stably expressing a Halo-taggedcGAS, cGAS formed puncta with fluorescein-labeled ISD in the cytoplasm (Fig. 2A and fig.S4A). To confirm that cGAS formed large granuleswith DNA in the cytoplasm, we used cGAS-deficient mouse embryonic fibroblast (MEF)cells reconstituted with green fluorescent pro-tein (GFP)–cGAS, transfected the cells with Cy5-ISD, and then permeabilized the cells withsaponin (22). cGAS formed puncta with ISD andremained in the cytoplasm after saponin treat-ment (Fig. 2B). The cGAS-DNA foci exhibitedliquidlike properties, as demonstrated by theability of two foci to fuse with each other (Fig.2C). Furthermore, upon photobleaching, cGASin the foci displayed near-complete fluorescencerecovery within 120 s (Fig. 2, D and E), indicatingthat cGAS exhibits dynamic liquidlike behaviorwithin cellular granules.To determine the functional consequence of

cGAS liquid droplet formation, we transfectedHeLa cells with herring testis DNA (HT-DNA)and measured cGAS activity in subcellular frac-tions (fig. S4B). Most cGAS activity was presentin the pellet obtained after centrifugation at2,000 × g (designated P2), which containsmainlythe nuclei and heavy particles (Fig. 2F). Furtherseparation of theP2 fractionby iodixanol (OptiPrep)density gradient ultracentrifugation revealed twodistinct pools of cGAS activity. The first pool wasin very heavy fractions (20 to 25% iodixanol)(Fig. 2G), which were separated from the nuclei(27.5 to 30% iodixanol). Thus, cGAS appearedto form heavy particles with transfected DNAthat were distinct from cellular organelles andvesicles and that contained active cGAS. Thesecond pool of cGAS activity was in fractions con-taining the nuclei. However, it remains to bedetermined whether this activity came fromcGAS within the nuclei or some cGAS particlesthat cosedimented with the nuclei. Similar re-sults were also obtained with human monocyticTHP-1 cells (fig. S4, C and D).Multivalent interactions drive liquid phase se-

paration (16). Long DNA has more binding sites(higher valency) for cGAS than short DNA, andfull-length cGAS (FL-cGAS) has higher valencyfor DNA than core cGAS (Fig. 3A) (6, 7, 11). Totest whether cGAS-DNA liquid phase separationis driven by the valency of cGAS and DNA inter-actions, we incubated FL-cGAS and N-terminallytruncated cGAS (DN146-cGAS, where the numeralindicates the number of amino acids deleted)with DNA of different lengths in the physiologicalbuffer (15 mM NaCl and 135 mM KCl) or a buffercontaining300mMNaCl.HumanFL-cGAS formedmore numerous and larger liquid droplets withlonger DNA (Fig. 3B). Both human and mouseFL-cGASs exhibited stronger phase separationthan N-terminally truncated cGAS with DNAof the same length either in the physiological

RESEARCH

Du et al., Science 361, 704–709 (2018) 17 August 2018 1 of 6

1Department of Molecular Biology, University of TexasSouthwestern Medical Center, Dallas, TX 75390-9148, USA.2Center for Inflammation Research, University of TexasSouthwestern Medical Center, Dallas, TX 75390-9148, USA.3Howard Hughes Medical Institute, University of TexasSouthwestern Medical Center, Dallas, TX 75390-9148, USA.*Corresponding author. Email: [email protected]

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Fig. 1. DNA binding to cGAS induces the formation of liquidlike dropletsin which cGAS is activated. (A) Schematic of hypothetical cGAS-DNAinteractions that drive liquid phase condensation. (B) Time-lapse imaging ofcGAS-DNA phase separation. Liquid droplets formed after mixing of 10 mMhuman FL-cGAS (3% was labeled with Alexa 488) with 10 mM 100-bp DNA(2% was labeled with Cy3) and matured over 60 min.The images shown arerepresentative of all fields in the well. (C) Time-lapse micrographs of mergingdroplets that formed as described in the legend to (B). Data are representative ofat least 10 merging droplets. (D) Fluorescence intensities of cGAS-DNA liquiddroplets forming over the time course of 120 min. Data were normalized to100% by maximal fluorescence intensity.Values shown are means ± SD. n = 4images. AF488, Alexa Fluor 488. (E) EqDiameter (the diameterof a circlewith thesame area as the measured object) frequency distribution of cGAS-DNA liquid

droplets formedat the indicated timepoints. cGAS, 5 mM;DNA, 5 mM. (F) FRAPofcGAS-DNA liquid droplets. Bleaching was performed at the indicated timepoints after cGAS (10 mM) and DNA (10 mM) were mixed, and the recoverywas allowed to occur at 25° or 37°C.Time 0 indicates the start of recovery afterphotobleaching. Shown are the means ± SD. n = 3 liquid droplets. n.s., notsignificant (P > 0.0332); ***P < 0.0002; ****P < 0.0001 [one-way analysis ofvariance (ANOVA)]. (G) Phase separation diagram of human FL-cGAS and100-bp DNA at the indicated concentrations. (H) (Left) cGAMP production bythe indicated concentrations of cGAS in the presence of ATP, GTP, andHT-DNA. cGAMP production at low cGAS concentrations is shown in the inset.(Right) Normalized cGAMP production divided by cGAS concentrations. Shownare the means ± SD. n = 3 assays. Data are representative of at least threeindependent experiments unless indicated to be otherwise.

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Fig. 2. DNA-induced liquid phase separation of cGAS in cells.(A) Representative live-cell images of cGAS-DNA puncta formationafter BJ cells stably expressing Halo-cGAS, which was covalentlylabeled with tetramethyl rhodamine, were transfected withfluorescein-ISD. Insets are zoomed images showing cGAS-DNApuncta. Scale bars, 10 mm. These images are representativeof at least 10 cells. (B) MEF cells stably expressing GFP-cGAS weretransfected with Cy5-ISD for 4 hours, after which they werepermeabilized with saponin and analyzed by fluorescencemicroscopy. Shown in blue is the plasma membrane markerwheat germ agglutinin. Arrows indicate puncta. Scale bars, 50 mm.These images are representative of at least five fields examined.(C) Time-lapse micrographs of cGAS (green) and DNA (magenta)puncta formation and fusion (time 0 represents 30 minafter transfection with Cy5–45-bp ISD). Arrows indicate puncta.Scale bar, 15 mm. The fusion events existed in all eight fieldsexamined. (D) Representative micrographs of cGAS-DNApuncta before and after photobleaching (arrow, bleach site).Scale bar, 15 mm. These images are representative of at least

three cells in which the cGAS-DNA puncta were photobleached.(E) Quantification of FRAP of cGAS-DNA puncta over a 120-s timecourse. K, exponential constant; R, normalized plateau afterfluorescence recovery. Shown are means ± SD. n = 3 cGAS-DNA puncta.(F) Subcellular fractionation of cGAS activity in cells transfectedwith DNA. HeLa cells transfected with HT-DNA or untransfectedHeLa cells were fractionated by differential centrifugation asdepicted in fig. S4B. Fractions were incubated with ATP and GTP,after which cGAMP was measured. Fractions were also analyzedby immunoblotting (IB) with antibodies against histone H2A(nuclear marker), glyceraldehyde-3-phosphate dehydrogenase(GAPDH) (cytoplasmic marker), or human cGAS (hcGAS).(G) The P2 fractions from (F) were further separated by OptiPrepgradient ultracentrifugation, and cGAS activity in differentfractions was measured as for (F). Fractions from cells nottransfected with DNA had no cGAS activity (upper panel).Error bars in (F) and (G) represent the variation range of duplicateassays. Data are representative of at least three independentexperiments.

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buffer (Fig. 3C) or at 300mMNaCl (fig. S5C). Theenzymatic activity of FL-cGAS in the presence ofHT-DNA was stronger than that of DN146-cGASin both low-salt buffer (Fig. 3D) and physiolog-ical buffer (Fig. 3E).To investigate the role of the cGAS N terminus

in cells, we reconstituted cGAS-deficient MEFcells with human FL-cGAS or DN160-cGAS (fig.S5F). After transfection with Cy5-ISD, FL-cGASformed puncta with Cy5-ISD in the MEF cells,whereas DN160-cGAS formed fewer puncta (Fig.3F and fig. S6). cGAMP production was alsohigher in cells stably expressing FL-cGAS than inthose expressing DN160-cGAS upon transfectionwith 45-bp ISD or HT-DNA (Fig. 3G; cGAS ex-pression levels are shown in fig. S5F).cGAS enzyme activity was much weaker in the

assay with physiological buffer than in the assaywith low-salt buffer (fig. S5, D and E). This raisesthe question of how cGAS is activated in cells.Wefound that zinc ions substantially promoted theactivity of recombinant cGAS in the physiologicalbuffer and that this enhancement could be par-tially replaced by other ions, such asMn2+ or Co2+

(Fig. 4A and fig. S7A), which is a general char-acteristic of enzymes that require zinc (23). Sim-ilarly, Zn2+ was the most efficient in activatingmouse cGAS (fig. S7, B and C). The optimal con-

centrations of Zn2+ were 160 to 625 mM (Fig. 4Aand fig. S7C), which is within the physiologicalconcentration range of zinc ions in cells (24, 25).Zn2+ at ~200 mM markedly facilitated DNA-induced cGAS phase separation at low concen-trations of cGAS and DNA (Fig. 4B and fig. S7D).Moreover, cGAS activity at low concentrationswas markedly enhanced in the presence of Zn2+

(Fig. 4C). At a concentration as low as 2.5 nM,which is below the concentration of cGAS in thecytoplasm of HeLa cells (approximately 8 to12 nM) (methods), cGAS underwent phase transi-tion and catalyzed cGAMP synthesis (Fig. 4, Band C). At 10 nM cGAS, 100-bp DNA activatedcGASwith amedian effective concentration (EC50)of ~1.4 nM, whereas 45-bp DNA hadmuchweakeractivity. DNA at 25 bp or shorter had no detect-able activity in the in vitro assay (Fig. 4D). ThisDNA length–dependent activation of cGAS waslargely mirrored in the cellular assay in whicha THP-1 reporter cell line was transfected withDNA (Fig. 4E).Using a thermal shift assay, we found that

DNA binding destabilized cGAS but that Zn2+

stabilized the cGAS-DNA complex (Fig. 4F andfig. S8A). Measurements of free Zn2+ concentra-tions revealed that Zn2+ bound to cGAS but notto DNA (Fig. 4G). To determine whether zinc

plays a role in cGAS activation within cells, wedepleted L929 cells of zinc with the zinc-specificchelatorN,N,N′,N′-tetrakis(2-pyridinylmethyl)-1,2-ethanediamine (TPEN). Cellular cGAMPproductionupon transfection with HT-DNA was decreasedin aTPENconcentration–dependentmanner (Fig.4H and fig. S8B). Under these conditions, TPENdid not affect the viability of L929 cells (fig. S8C).Live-cell imaging with a zinc-specific fluorescentprobe revealed that cGAS-DNApuncta containedzinc (fig. S8, D and E). These results showed thatzinc facilitated cGAS activation in cells by promot-ing cGAS phase transition in the presence ofcytosolic DNA.Thus, DNA binding to cGAS induces a robust

phase transition to liquidlike droplets, which func-tion as microreactors in which the enzyme andreactants are concentrated to greatly enhancethe production of cGAMP. ThismechanismallowscGAS to detect the presence of DNA in the cyto-plasm above a certain threshold to trigger aswitchlike response. Such a switchlike responseis made possible by the multivalent interactionsbetween the DNA binding domains of cGASand DNA in a manner that depends on the DNAlength. This also provides an explanation forwhy long DNA activates cGAS more efficiently.The binding between cGAS and DNA involves

Du et al., Science 361, 704–709 (2018) 17 August 2018 4 of 6

Fig. 3. Multivalent interactions drivecGAS-DNA condensation and promotecGAS activation. (A) Schematic ofhypothetical cGAS and DNA valencies.(B) Representative images of phaseseparation by mixing of cGAS (10 mM) withdsDNA of different lengths (10 mM) inphysiological buffer. Scale bar, 10 mm.(C) Bright-field images of phase separationby mixing of DNA of different lengthswith full-length or N-terminally truncatedhuman or mouse cGAS as indicated. Scalebar, 20 mm. The images shown in (B) and(C) are representative of all fields in thewells. (D and E) cGAMP production bydifferent concentrations of recombinanthuman FL-cGAS or N-terminally truncatedcGAS in low-salt buffer (D) or physiologicalbuffer (E). Shown are the means ± SD.n = 3 assays. (F) Quantification ofcGAS-DNA puncta by imaging of MEFcells expressing GFP-tagged humanFL-cGAS or DN160-cGAS after transfectionwith Cy5-ISD. Representative imagesare shown in fig. S6. Values shown aremeans ± SD. n = 5 images. (G) cGAMPproduction in the MEF cells expressinghuman FL-cGAS or DN160-cGAS aftertransfection with ISD or HT-DNA. Values aremeans ± SD. n = 3. (F) and (G): ****P <0.0001 (multiple t tests). cGAS expressionlevels are shown in fig. S5F. Data arerepresentative of at least threeindependent experiments.

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extensive ionic interactions between the positivelycharged surfaces of cGAS and negatively chargedDNA. Such interactions are vulnerable to cyto-plasmic salt concentrations, which may be amechanism to prevent spurious activation ofcGAS by self-DNA below a certain threshold.However, we found that zinc ions could substan-tially enhance cGAS phase separation and itsenzymatic activation at physiological salt con-centrations. Free zinc ions are stored mainly inorganelles such as the mitochondria and theendoplasmic reticulum (26), and their deliveryto the cytosol may be another avenue by whichcGAS activity is regulated in cells. DNA bindingto cGAS induced formation of cGAS-DNA con-densates, which were observed as cytoplasmicfoci within cells. Further characterization of thedynamics and composition of the cGAS con-densates should provide deeper insights into themechanism by which cGAS activity is tightly reg-

ulated to trigger an appropriate immune responseto pathogens while simultaneously avoiding auto-immune reactions to self-tissues.

REFERENCES AND NOTES

1. L. Sun, J. Wu, F. Du, X. Chen, Z. J. Chen, Science 339, 786–791(2013).

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(2016).6. L. Andreeva et al., Nature 549, 394–398 (2017).7. X. Zhang et al., Cell Rep. 6, 421–430 (2014).8. P. J. Kranzusch, A. S. Lee, J. M. Berger, J. A. Doudna, Cell Rep.

3, 1362–1368 (2013).9. P. Gao et al., Cell 153, 1094–1107 (2013).10. F. Civril et al., Nature 498, 332–337 (2013).11. X. Li et al., Immunity 39, 1019–1031 (2013).12. C. P. Brangwynne et al., Science 324, 1729–1732 (2009).13. C. P. Brangwynne, T. J. Mitchison, A. A. Hyman, Proc. Natl.

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17. Y. Shin, C. P. Brangwynne, Science 357, eaaf4382 (2017).18. T. W. Han et al., Cell 149, 768–779 (2012).19. M. Kato et al., Cell 149, 753–767 (2012).20. P. Li et al., Nature 483, 336–340 (2012).21. Y. Lin, D. S. Protter, M. K. Rosen, R. Parker, Mol. Cell 60,

208–219 (2015).22. P. Seeman, D. Cheng, G. H. Iles, J. Cell Biol. 56, 519–527

(1973).23. I. Bertini, H. B. Gray, S. J. Lippard, J. S. Valentine, Bioinorganic

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ACKNOWLEDGMENTS

We thank H. Yang for generating the MEFcGAS KO-GFP-cGAS andMEFcGAS KO-GFP-DN160cGAS cell lines, L. Sun for helping withcGAMP bioassays, C. Zhang for helping with live-cell imaging, and

Du et al., Science 361, 704–709 (2018) 17 August 2018 5 of 6

Fig. 4. Zinc ions promote DNA-induced phaseseparation and activation of cGAS. (A) Zn2+

enhances cGAS activation in vitro. Recombinanthuman FL-cGAS (15 nM) was incubated withATP, GTP, and DNA in a physiological buffercontaining the indicated concentrations of Zn2+,and cGAMP production was measured.(B) Quantification of cGAS-DNA condensatesin the presence or absence of zinc. Liquid-phasecondensates formed after mixing of AlexaFluor 488–labeled human FL-cGAS with 45-bpCy3-labeled ISD at the indicated concentrationsof each in physiological buffer with or withoutZn2+ (200 mM). Images were then captured byconfocal microscopy, and representative imagesare shown in fig. S7D. Values are means ± SD.n = 5 images. P values are from multiple t tests.(C) cGAMP production in physiological buffercontaining HT-DNA and different concentrationsof cGAS in the presence or absence of Zn2+

(200 mM). The activity of cGAS at lowconcentrations is shown in the inset. P valuesare from multiple t tests. (D) cGAMPproduction by 10 nM cGAS in physiologicalbuffer containing 200 mM Zn2+ and differentconcentrations of DNA of the indicated lengths.(E) THP-1–Lucia ISG cells, which harbor aluciferase gene under the ISG54 promoter, weretransfected with the indicated DNA for 24 hours,after which the secreted luciferase activitywas measured. RLU, relative luciferase units.(F) Thermal shift assay to measure the stabilityof cGAS or the cGAS-DNA complex in thepresence or absence of Zn2+ (200 mM). Tm,protein melting temperature. Values aremeans ± SD. n = 3. P values are from anunpaired t test. (G) Measurement of cGASbinding to zinc. Zinc ions (10 mM) were incubated with various concen-trations of DNA, cGAS, or both, and the solution was passed through acentrifugal filter, after which the zinc ion concentration in the filtrate wasmeasured. The dissociation constant (Kd) values for zinc binding tocGAS and the cGAS-DNA complex were 3.9 ± 1.3 mM and 3.0 ± 0.4 mM,respectively. (H) Depletion of intracellular zinc inhibits cGAS activation byDNA. L929 cells were incubated with the indicated concentrations

of the Zn2+ chelator TPEN for 2 hours before transfection with HT-DNA.cGAMP production was measured by a bioassay. Images depictingintracellular zinc depletion are shown in fig. S8B. (B), (C), and (F):n.s., P > 0.0332; *P < 0.0332; **P < 0.0021; ***P < 0.0002;****P < 0.0001. Error bars represent the variation range of duplicateassays unless otherwise indicated. Data are representative of atleast three independent experiments.

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S. Banani for discussions regarding liquid-liquid phase separationof proteins. Funding: This work was supported by grants from theLupus Research Alliance, the Cancer Prevention and ResearchInstitute of Texas (RP120718 and RP150498), and the WelchFoundation (I-1389). Z.J.C. is an investigator of the Howard HughesMedical Institute. Author contributions: M.D. designed andperformed experiments. M.D. and Z.J.C. wrote and revised themanuscript. Competing interests: All authors declare no conflicts

of interest. Data and materials availability: All data needed toevaluate the conclusions in this paper are present either in themain text or in the supplementary materials.

SUPPLEMENTARY MATERIALS

www.sciencemag.org/content/361/6403/704/suppl/DC1Materials and Methods

Figs. S1 to S8Table S1References (27–30)Movie S1

24 January 2018; accepted 27 June 2018Published online 5 July 201810.1126/science.aat1022

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DNA-induced liquid phase condensation of cGAS activates innate immune signalingMingjian Du and Zhijian J. Chen

originally published online July 5, 2018DOI: 10.1126/science.aat1022 (6403), 704-709.361Science 

, this issue p. 704; see also p. 646Scienceinterferon responses.

STING-dependentmanner. Binding triggers a switchlike reaction that concentrates the enzyme and reactants to enhance multivalent interactions, augmented by zinc, between DNA binding domains on cGAS and DNA in a length-dependentresults in liquid droplets containing activated cGAS (see the Perspective by Ablasser). This phenomenon occurs through

AMP synthase (cGAS),−compartments. Du and Chen show that DNA binding to its cytoplasmic sensor, cyclic GMP formation of cellular bodies from P granules to nucleoli. Essentially, dense-phase liquid droplets act like cellular

Spontaneous partitioning of a homogeneous solution of molecules, or liquid-phase separation, underlies theLiquid droplets step on the cGAS

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