@article{mbs:/content/journal/micro/10.1099/mic.0.078402-0, author = "Rodríguez-Lombardero, Silvia and Vizoso-Vázquez, Ángel and Lombardía, Luis J. and Becerra, Manuel and González-Siso, M. Isabel and Cerdán, M. Esperanza", title = "Sky1 regulates the expression of sulfur metabolism genes in response to cisplatin", journal= "Microbiology", year = "2014", volume = "160", number = "7", pages = "1357-1368", doi = "https://doi.org/10.1099/mic.0.078402-0", url = "https://www.microbiologyresearch.org/content/journal/micro/10.1099/mic.0.078402-0", publisher = "Microbiology Society", issn = "1465-2080", type = "Journal Article", abstract = "Cisplatin is commonly used in cancer therapy and yeast cells are also sensitive to this compound. We present a transcriptome analysis discriminating between RNA changes induced by cisplatin treatment, which are dependent on or independent of SKY1 function – a gene whose deletion increases resistance to the drug. Gene expression changes produced by addition of cisplatin to W303 and W303-Δsky1 cells were recorded using DNA microarrays. The data, validated by quantitative PCR, revealed 122 differentially expressed genes: 69 upregulated and 53 downregulated. Among the upregulated genes, those related to sulfur metabolism were over-represented and partially dependent on Sky1. Deletions of MET4 or other genes encoding co-regulators of the expression of sulfur-metabolism-related genes, with the exception of MET28, did not modify the cisplatin sensitivity of yeast cells. One of the genes with the highest cisplatin-induced upregulation was SEO1, encoding a putative permease of sulfur compounds. We also measured the platinum, sulfur and glutathione content in W303, W303-Δsky1 and W303-Δseo1 cells after cisplatin treatment, and integration of the data suggested that these transcriptional changes might represent a cellular response that allowed chelation of cisplatin with sulfur-containing amino acids and also helped DNA repair by stimulating purine biosynthesis. The transcription pattern of stimulation of sulfur-containing amino acids and purine synthesis decreased, or even disappeared, in the W303-Δsky1 strain.", }