{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T23:20:04Z","timestamp":1778109604342,"version":"3.51.4"},"reference-count":77,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"6784","funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["Project-ID 393547839"],"award-info":[{"award-number":["Project-ID 393547839"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB 1361"],"award-info":[{"award-number":["SFB 1361"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Dr. Rolf M. Schweite Stiftung","award":["project 13\/2017"],"award-info":[{"award-number":["project 13\/2017"]}]},{"name":"Hessian Ministry for Science and the Art","award":["Cluster project ENABLE"],"award-info":[{"award-number":["Cluster project ENABLE"]}]},{"name":"Croatian Science Foundation grants","award":["P-2020-02-8921 and DOK-2018-01- 1571"],"award-info":[{"award-number":["P-2020-02-8921 and DOK-2018-01- 1571"]}]},{"name":"Rising Star Award from the European Association of Cancer Research and the Pezzcoler and Mark Foundations, and the European Research Council .","award":["Starting Grant \u201cMitErrA\u201d"],"award-info":[{"award-number":["Starting Grant \u201cMitErrA\u201d"]}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB 1531 \u2013 project number 456687919"],"award-info":[{"award-number":["SFB 1531 \u2013 project number 456687919"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Cluster4Future PROXIDRUGS, funded by the Federal Ministry of Research, Techology and Spac","award":["BMFTR (03ZU2109CA)"],"award-info":[{"award-number":["BMFTR (03ZU2109CA)"]}]},{"name":"Louise Jeantet award"}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Science"],"published-print":{"date-parts":[[2026,1,29]]},"abstract":"<jats:p>\n                    DNA-protein cross-links (DPCs) are highly toxic DNA lesions that block replication and transcription, but their impact on organismal physiology is unclear. We identified a role for the metalloprotease SPRTN in preventing DPC-driven immunity and its pathological consequences. Loss of SPRTN activity during replication and mitosis lead to unresolved DNA damage, chromosome segregation errors, micronuclei formation, and cytosolic DNA release that activates the cyclic GMP-AMP synthase (cGAS)\u2013stimulator of interferon genes (STING) pathway. In a\n                    <jats:italic toggle=\"yes\">Sprtn<\/jats:italic>\n                    knock-in mouse model of Ruijs-Aalfs progeria syndrome, chronic cGas-Sting signaling caused embryonic lethality through inflammation and innate immune responses. Surviving mice displayed aging phenotypes beginning in embryogenesis, which persisted into adulthood. Genetic or pharmacological inhibition of cGas-Sting rescued embryonic lethality and alleviated progeroid phenotypes.\n                  <\/jats:p>","DOI":"10.1126\/science.adx9445","type":"journal-article","created":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T19:01:14Z","timestamp":1769713274000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":3,"title":["DNA-protein cross-links promote cGAS-STING\u2013driven premature aging and embryonic lethality"],"prefix":"10.1126","volume":"391","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-3908-7127","authenticated-orcid":true,"given":"Ines","family":"Tomaskovic","sequence":"first","affiliation":[{"name":"Institute of Biochemistry II, Faculty of Medicine, Goethe University Frankfurt, Frankfurt, Germany."}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7576-1061","authenticated-orcid":true,"given":"Cristian","family":"Prieto-Garcia","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry II, Faculty of Medicine, Goethe University Frankfurt, Frankfurt, Germany."}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7701-0643","authenticated-orcid":true,"given":"Maria","family":"Boskovic","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry II, Faculty of Medicine, Goethe University Frankfurt, Frankfurt, Germany."},{"name":"Laboratory for Cancer Research, University of Split School of Medicine, Split, Croatia."}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5597-7431","authenticated-orcid":true,"given":"Mateo","family":"Glumac","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry II, Faculty of Medicine, Goethe University Frankfurt, Frankfurt, Germany."},{"name":"Laboratory for Cancer Research, University of Split School of Medicine, Split, Croatia."}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7997-446X","authenticated-orcid":true,"given":"Tsung-Lin","family":"Tsai","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology (IMB), Mainz, Germany."}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1800-2680","authenticated-orcid":true,"given":"Thorsten","family":"Mosler","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry II, Faculty of Medicine, Goethe University Frankfurt, Frankfurt, Germany."},{"name":"Institute of Molecular Biology (IMB), Mainz, Germany."}]},{"given":"Rubina","family":"Kazi","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry II, Faculty of Medicine, Goethe University Frankfurt, Frankfurt, Germany."}]},{"given":"Rajeshwari","family":"Rathore","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry II, Faculty of Medicine, Goethe University Frankfurt, Frankfurt, Germany."}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4577-8620","authenticated-orcid":true,"given":"Jorge","family":"Andrade","sequence":"additional","affiliation":[{"name":"Angiogenesis &amp; Metabolism Laboratory, Center of Vascular Biomedicine, Berlin Institute of Health at Charit\u00e9-Universit\u00e4tsmedizin Berlin, Berlin, Germany."},{"name":"Max Delbr\u00fcck Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany."}]},{"given":"Marina","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry II, Faculty of Medicine, Goethe University Frankfurt, Frankfurt, Germany."}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4648-0076","authenticated-orcid":true,"given":"Giulio","family":"Giuliani","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry II, Faculty of Medicine, Goethe University Frankfurt, Frankfurt, Germany."},{"name":"Buchmann Institute for Molecular Life Sciences, Goethe University Frankfurt, Frankfurt, Germany."}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8761-1514","authenticated-orcid":true,"given":"Anne-Claire","family":"Jacomin","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry II, Faculty of Medicine, Goethe University Frankfurt, Frankfurt, Germany."},{"name":"Buchmann Institute for Molecular Life Sciences, Goethe University Frankfurt, Frankfurt, Germany."}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9863-6538","authenticated-orcid":true,"given":"Raquel S.","family":"Pereira","sequence":"additional","affiliation":[{"name":"Georg-Speyer-Haus Institute for Tumor Biology and Experimental Medicine and Goethe University Frankfurt, Frankfurt, Germany."}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4941-9759","authenticated-orcid":true,"given":"Elias","family":"Knop","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry II, Faculty of Medicine, Goethe University Frankfurt, Frankfurt, Germany."}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1701-9384","authenticated-orcid":true,"given":"Laurens","family":"Wachsmuth","sequence":"additional","affiliation":[{"name":"Institute for Genetics, University of Cologne, Cologne, Germany."}]},{"given":"Petra","family":"Beli","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology (IMB), Mainz, Germany."}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0573-6239","authenticated-orcid":true,"given":"Koraljka","family":"Husnjak","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry II, Faculty of Medicine, Goethe University Frankfurt, Frankfurt, Germany."}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9870-0966","authenticated-orcid":true,"given":"Manolis","family":"Pasparakis","sequence":"additional","affiliation":[{"name":"Institute for Genetics, University of Cologne, Cologne, Germany."},{"name":"Cologne Excellence Cluster for Aging and Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany"},{"name":"Germany. Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8475-8999","authenticated-orcid":true,"given":"Andrea","family":"Ablasser","sequence":"additional","affiliation":[{"name":"Global Health Institute, Swiss Federal Institute of Technology Lausanne (EPFL), Lausanne, Switzerland."}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3603-1119","authenticated-orcid":true,"given":"Daniela S.","family":"Krause","sequence":"additional","affiliation":[{"name":"Institute of Transfusion Medicine, Transfusion Center, University Medicine Mainz, Mainz, Germany."},{"name":"Research Center for Immunotherapy (FZI), University Medical Center, University of Mainz, Mainz, Germany."},{"name":"German Cancer Research Center (DKFZ), Heidelberg, Germany."},{"name":"German Cancer Consortium (DKTK), Germany."}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5689-0036","authenticated-orcid":true,"given":"Michael","family":"Potente","sequence":"additional","affiliation":[{"name":"Angiogenesis &amp; Metabolism Laboratory, Center of Vascular Biomedicine, Berlin Institute of Health at Charit\u00e9-Universit\u00e4tsmedizin Berlin, Berlin, Germany."},{"name":"Max Delbr\u00fcck Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany."}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6969-044X","authenticated-orcid":true,"given":"Stamatis","family":"Papathanasiou","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology (IMB), Mainz, Germany."}]},{"given":"Janos","family":"Terzic","sequence":"additional","affiliation":[{"name":"Laboratory for Cancer Research, University of Split School of Medicine, Split, Croatia."}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8156-9511","authenticated-orcid":true,"given":"Ivan","family":"Dikic","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry II, Faculty of Medicine, Goethe University Frankfurt, Frankfurt, Germany."},{"name":"Buchmann Institute for Molecular Life Sciences, Goethe University Frankfurt, Frankfurt, Germany."}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.04.053"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2016.09.032"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2007.07.029"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaf638"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2059-5"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04133-7"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3103"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-020-01539-3"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6744"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.21491"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-024-01391-1"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2016.09.031"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.10730"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx107"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0135-6"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2014.06.003"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1100040"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03307-7"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2022.101976"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-35988-1"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.110080"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2019.11.006"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.2395"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2001760117"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.add4920"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2021.10.015"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2020107413"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-18377-w"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06157-7"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.09.048"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2024.02.001"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.08.020"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.3390\/genes11040409"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature23449"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1232458"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07317"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.03.056"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2065"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.110814"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04421-w"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-021-00524-z"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2020.10.012"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abd7197"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-020-00624-8"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0287-8"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202103837"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.06.028"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1705499114"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2017.05.022"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature23470"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-023-00420-x"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2014.07.010"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-024-01401-2"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-024-01394-y"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03523-2"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2089"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.adj8691"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad022"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201911101"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201911101"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1021\/pr3000249"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth1060"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1511"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1021\/pr101065j"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth1019"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.18.3442"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4256"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-020-0912-y"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcpro.2021.100077"},{"key":"e_1_3_2_71_2","doi-asserted-by":"crossref","unstructured":"Y. Hsiao H. Zhang G. X. Li Y. Deng F. Yu H. V. Kahrood J. R. Steele R. B. Schittenhelm A. I. Nesvizhskii Analysis and visualization of quantitative proteomics data using FragPipe-Analyst. J Proteome Res 23 4c00294 (2024). 10.1016\/j.mcpro.2021.10007733813065","DOI":"10.1101\/2024.03.05.583643"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1021\/ac502040v"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv007"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506580102"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-021-00875-z"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.adi5295"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.xpro.2020.100086"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.749203"}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.adx9445","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T19:02:09Z","timestamp":1769713329000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.adx9445"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,29]]},"references-count":77,"journal-issue":{"issue":"6784","published-print":{"date-parts":[[2026,1,29]]}},"alternative-id":["10.1126\/science.adx9445"],"URL":"https:\/\/doi.org\/10.1126\/science.adx9445","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,29]]},"assertion":[{"value":"2025-04-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-24","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadx9445"}}