{"id":8084,"date":"2025-11-19T16:00:00","date_gmt":"2025-11-19T16:00:00","guid":{"rendered":"http:\/\/sebigec.es\/blog\/?guid=18f86e9d007335559eb0e1ce2536cf06"},"modified":"2025-11-19T23:00:00","modified_gmt":"2025-11-19T23:00:00","slug":"breaking-the-script-transcriptional-addiction-as-a-driver-of-genome-instability-in-cancer","status":"publish","type":"post","link":"https:\/\/sebigec.es\/blog\/index.php\/2025\/11\/19\/breaking-the-script-transcriptional-addiction-as-a-driver-of-genome-instability-in-cancer\/","title":{"rendered":"Breaking the script: transcriptional addiction as a driver of genome instability in cancer"},"content":{"rendered":"Transcription is not only an essential cellular process but also a major source of endogenous DNA strand breaks. Many cancers exhibit transcriptional addiction and rely on dysregulated and excessive transcription to maintain the malignant state. We review recent advances in transcription-associated DNA breaks and their role as an essential player in endogenous fragility. We highlight the contrast between replication-dependent transcriptional breaks (e.g., transcription\u2013replication conflicts) and replication-independent transcriptional breaks (resulting from transcription itself). We outline two types of transcriptional double-strand breaks (DSBs): promoter-associated breaks that are linked to gene activation, and gene-body breaks that occur stochastically from transcription byproducts. We discuss how supercoiling, R-loops, and enhancer\u2013promoter looping at super-enhancer (SE)-regulated loci can increase DNA fragility and thereby create a distinct Achilles\u2019 heel, and propose that targeting the coupling between SE-driven transcription and DNA repair could offer new therapeutic strategies for cancer.","protected":false},"excerpt":{"rendered":"<p>Transcription is not only an essential cellular process but also a major source of endogenous DNA strand breaks. Many cancers exhibit transcriptional addiction and rely on dysregulated and excessive transcription to maintain the malignant state. We rev&#8230;<\/p>\n","protected":false},"author":387,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[6,65],"tags":[79],"class_list":["post-8084","post","type-post","status-publish","format-standard","hentry","category-articulos","category-trends-in-genetics","tag-trendsgen"],"_links":{"self":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/8084","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/users\/387"}],"replies":[{"embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/comments?post=8084"}],"version-history":[{"count":24,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/8084\/revisions"}],"predecessor-version":[{"id":8152,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/8084\/revisions\/8152"}],"wp:attachment":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/media?parent=8084"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/categories?post=8084"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/tags?post=8084"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}