{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:16:27Z","timestamp":1791994587374,"version":"4.4.0"},"reference-count":33,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2017,5,1]],"date-time":"2017-05-01T00:00:00Z","timestamp":1493596800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Tumour Biol."],"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:p>Cellular senescence is a key physiological barrier against tumor and represents an option for therapeutic intervention. One pivotal intracellular stimulus causing senescence is DNA damage response, while the senescence-associated heterochromatin in cancer limits the strength of the DNA damage response to endogenous genotoxic stress or DNA-damaging agents. Therefore, targeting the maintenance of compacted chromatin in cancer cells represents an optional intervention to improve the therapeutic efficacy in cancer treatment. Given a crosstalk between methionine cycle and histone methylation, we hypothesize that pharmacologically disrupting methylation potential, defined as the ratio of cellular S-adenosylmethionine to S-adenosylhomocysteine, could affect the chromatin structures in cancer cells and thus enhance their sensitivity to DNA damage response signaling. Our results showed that 3-deazaneplanocin A, a chemical inhibitor of S-adenosylhomocysteine hydrolase, elicited a typical cellular senescence in hepatoma cells. Therapy-induced senescence by 3-deazaneplanocin A was mediated through p53\u2013p21 pathway and triggered by enhanced ataxia-telangiectasia mutated activation related to chromatin changes. In conclusion, our study demonstrated that metabolic perturbation of chromatin status in oncogene-activated cancers could be an optional intervention to sensitize DNA damage response signaling.<\/jats:p>","DOI":"10.1177\/1010428317699117","type":"journal-article","created":{"date-parts":[[2017,5,1]],"date-time":"2017-05-01T06:24:55Z","timestamp":1493619895000},"page":"101042831769911","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":17,"title":["Metabolic perturbation of epigenome by inhibiting\n                    <i>S<\/i>\n                    -adenosylhomocysteine hydrolase elicits senescence through DNA damage response in hepatoma cells"],"prefix":"10.1177","volume":"39","author":[{"given":"Guozhen","family":"Wu","sequence":"first","affiliation":[{"name":"Clinical School, The Third Central Hospital of Tianjin, Tianjin Medical University, Tianjin, China"},{"name":"Department of Hepatobiliary Surgery, The Third 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