1887

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 function – a gene whose deletion increases resistance to the drug. Gene expression changes produced by addition of cisplatin to W303 and W303-Δ 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 or other genes encoding co-regulators of the expression of sulfur-metabolism-related genes, with the exception of , did not modify the cisplatin sensitivity of yeast cells. One of the genes with the highest cisplatin-induced upregulation was , encoding a putative permease of sulfur compounds. We also measured the platinum, sulfur and glutathione content in W303, W303-Δ and W303-Δ 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-Δ strain.

Funding
This study was supported by the:
  • MICINN (Spain) co-financed by FEDER (CEE) (Award BFU2009-08854)
  • Xunta de Galicia (Award D.O.G. 10-10-2012. EN: 2012/118 and D.O.G. 3-12-2008 EN: 2008/008)
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2014-07-01
2021-04-20
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