{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:45:30Z","timestamp":1791229530739,"version":"4.1.0"},"reference-count":71,"publisher":"Canadian Science Publishing","issue":"1","license":[{"start":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T00:00:00Z","timestamp":1706745600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/deed.en_GB"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"crossref","award":["RGPIN 2020-04034"],"award-info":[{"award-number":["RGPIN 2020-04034"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["cdnsciencepub.com"],"crossmark-restriction":false},"short-container-title":["Biochem. Cell Biol."],"published-print":{"date-parts":[[2024,2,1]]},"abstract":"<jats:p>The cGAS-STING (cyclic GMP\u2013AMP synthase (cGAS)\u2013stimulator of interferon genes (STING)) axis integrates DNA damage and cellular stress with type I interferon (IFN) signalling to facilitate transcriptional changes underlying inflammatory stress responses. The cGAS-STING pathway responds to cytosolic DNA in the form of double-stranded DNA, micronuclei, and long interspersed nuclear element 1 (L1) retroelements. L1 retroelements are a class of self-propagating non-long terminal repeat transposons that have remained highly active in mammalian genomes. L1 retroelements are emerging as important inducers of cGAS-STING and IFN signalling, which are often dysregulated in several diseases, including cancer. A key repressor of cGAS-STING and L1 activity is the exonuclease three prime repair exonuclease 1 (TREX1), and loss of TREX1 promotes the accumulation of L1. In addition, L1 dysregulation is a common theme among diseases with chronic induction of type I IFN signalling through cGAS-STING, such as Aicardi\u2013Gouti\u00e8res syndrome, Fanconi anemia, and dermatomyositis. Although TREX1 is highly conserved in tetrapod species, other suppressor proteins exist that inhibit L1 retrotransposition. These suppressor genes when mutated are often associated with diseases characterized by unchecked inflammation that is associated with high cGAS-STING activity and elevated levels of L1 expression. In this review, we discuss these interconnected pathways of L1 suppression and their role in the regulation of cGAS-STING and inflammation in disease.<\/jats:p>","DOI":"10.1139\/bcb-2023-0134","type":"journal-article","created":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T17:35:15Z","timestamp":1693330515000},"page":"38-46","update-policy":"https:\/\/doi.org\/10.1139\/csp-crossmark-policy","source":"Crossref","is-referenced-by-count":50,"title":["LINE-1: an emerging initiator of cGAS-STING signalling and inflammation that is dysregulated in disease"],"prefix":"10.1139","volume":"102","author":[{"given":"Sabateeshan","family":"Mathavarajah","sequence":"first","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, Dalhousie University","place":["Halifax, 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