Doxorubicin induces an extensive transcriptional and metabolic rewiring in yeast cells

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dc.WoS.categoriesMultidisciplinary Sciencesen_US
dc.contributor.authorNikerel, Hilal Taymaz
dc.date.accessioned2020-06-12T08:52:24Z
dc.date.available2020-06-12T08:52:24Z
dc.date.issued2018-10-12
dc.description.abstractDoxorubicin is one of the most effective chemotherapy drugs used against solid tumors in the treatment of several cancer types. Two different mechanisms, (i) intercalation of doxorubicin into DNA and inhibition of topoisomerase II leading to changes in chromatin structure, (ii) generation of free radicals and oxidative damage to biomolecules, have been proposed to explain the mode of action of this drug in cancer cells. A genome-wide integrative systems biology approach used in the present study to investigate the long-term effect of doxorubicin in Saccharomyces cerevisiae cells indicated the up-regulation of genes involved in response to oxidative stress as well as in Rad53 checkpoint sensing and signaling pathway. Modular analysis of the active sub-network has also revealed the induction of the genes significantly associated with nucleosome assembly/disassembly and DNA repair in response to doxorubicin. Furthermore, an extensive re-wiring of the metabolism was observed. In addition to glycolysis, and sulfate assimilation, several pathways related to ribosome biogenesis/translation, amino acid biosynthesis, nucleotide biosynthesis, de novo IMP biosynthesis and one-carbon metabolism were significantly repressed. Pentose phosphate pathway, MAPK signaling pathway biological processes associated with meiosis and sporulation were found to be induced in response to long-term exposure to doxorubicin in yeast cells.en_US
dc.fullTextLevelFull Texten_US
dc.identifier.doi10.1038/s41598-018-31939-9
dc.identifier.issn2045-2322
dc.identifier.pmid30209405en_US
dc.identifier.scopus2-s2.0-85053241255en_US
dc.identifier.urihttps://hdl.handle.net/11411/2203
dc.identifier.urihttps://doi.org/10.1038/s41598-018-31939-9
dc.identifier.wosWOS:000444376500005en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.nationalInternationalen_US
dc.numberofauthors4en_US
dc.publisherNATURE PUBLISHING GROUPen_US
dc.relation.ispartofSCIENTIFIC REPORTSen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectOPOISOMERASE-IIen_US
dc.subjectSACCHAROMYCES-CEREVISIAEen_US
dc.subjectFUNCTIONAL-ANALYSISen_US
dc.subjectSYSTEMS BIOLOGYen_US
dc.subjectCYCLE ARRESTen_US
dc.subjectDNA-DAMAGEen_US
dc.subjectCANCERen_US
dc.subjectEXPRESSIONen_US
dc.subjectGENEen_US
dc.subjectANTICANCERen_US
dc.titleDoxorubicin induces an extensive transcriptional and metabolic rewiring in yeast cells
dc.typeArticle
dc.volume8en_US

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