Time-dependent re-organization of biological processes by the analysis of the dynamic transcriptional response of yeast cells to doxorubicin

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dc.authoridKarabekmez, Muhammed Erkan/0000-0002-0517-5227|Kirdar, Betul/0000-0002-3289-3216
dc.contributor.authorKarabekmez, Muhammed Erkan
dc.contributor.authorTaymaz-Nikerel, Hilal
dc.contributor.authorEraslan, Serpil
dc.contributor.authorKirdar, Betul
dc.date.accessioned2024-07-18T20:56:58Z
dc.date.available2024-07-18T20:56:58Z
dc.date.issued2021
dc.departmentİstanbul Bilgi Üniversitesien_US
dc.description.abstractDoxorubicin is an efficient chemotherapeutic reagent in the treatment of a variety of cancers. However, its underlying molecular mechanism is not fully understood and several severe side effects limit its application. In this study, the dynamic transcriptomic response of Saccharomyces cerevisiae cells to a doxorubicin pulse in a chemostat system was investigated to reveal the underlying molecular mechanism of this drug. The clustering of differentially and significantly expressed genes (DEGs) indicated that the response of yeast cells to doxorubicin is time dependent and may be classified as short-term, mid-term and long-term responses. The cells have started to reorganize their response after the first minute following the injection of the pulse. A modified version of Weighted Gene Co-expression Network Analysis (WGCNA) was used to cluster the positively correlated co-expression profiles, and functional enrichment analysis of these clusters was carried out. DNA replication and DNA repair processes were significantly affected and induced 60 minutes after exposure to doxorubicin. The response to oxidative stress was not identified as a significant term. A transcriptional re-organization of the metabolic pathways seems to be an early event and persists afterwards. The present study reveals for the first time that the RNA surveillance pathway, which is a post-transcriptional regulatory pathway, may be implicated in the short-term reaction of yeast cells to doxorubicin. Integration with regulome revealed the dynamic re-organization of the transcriptomic landscape. Fhl1p, Mbp1p, and Mcm1p were identified as primary regulatory factors responsible for tuning the differentially expressed genes.en_US
dc.description.sponsorshipBogazici University Research Fund (BAP) [8660]en_US
dc.description.sponsorshipThis work was supported by Bogazici University Research Fund (BAP) [grant number 8660].en_US
dc.identifier.doi10.1039/d1mo00046b
dc.identifier.endpage582en_US
dc.identifier.issn2515-4184
dc.identifier.issue4en_US
dc.identifier.pmid34095940en_US
dc.identifier.scopus2-s2.0-85112361756en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.startpage572en_US
dc.identifier.urihttps://doi.org/10.1039/d1mo00046b
dc.identifier.urihttps://hdl.handle.net/11411/8931
dc.identifier.volume17en_US
dc.identifier.wosWOS:000658404100001en_US
dc.identifier.wosqualityQ3en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherRoyal Soc Chemistryen_US
dc.relation.ispartofMolecular Omicsen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectSaccharomyces-Cerevisiaeen_US
dc.subjectMessenger-Rnasen_US
dc.subjectGeneen_US
dc.subjectExpressionen_US
dc.subjectActivationen_US
dc.subjectResistanceen_US
dc.subjectPathwayen_US
dc.subjectHearten_US
dc.subjectModelen_US
dc.subjectCardiotoxicityen_US
dc.titleTime-dependent re-organization of biological processes by the analysis of the dynamic transcriptional response of yeast cells to doxorubicin
dc.typeArticle

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