Abstract
In the traditional fermentative model yeast Saccharomyces cerevisiae, ScIxr1 is an HMGB (High Mobility Group box B) protein that has been considered as an important regulator of gene transcription in response to external changes like oxygen, carbon source, or nutrient availability. Kluyveromyces lactis is also a useful eukaryotic model, more similar to many human cells due to its respiratory metabolism. We cloned and functionally characterized by different methodologies KlIXR1, which encodes a protein with only 34.4% amino acid sequence similarity to ScIxr1. Our data indicate that both proteins share common functions, including their involvement in the response to hypoxia or oxidative stress induced by hydrogen peroxide or metal treatments, as well as in the control of key regulators for maintenance of the dNTP (deoxyribonucleotide triphosphate) pool and ribosome synthesis. KlIxr1 is able to bind specific regulatory DNA sequences in the promoter of its target genes, which are well conserved between S. cerevisiae and K. lactis. Oppositely, we found important differences between ScIrx1 and KlIxr1 affecting cellular responses to cisplatin or cycloheximide in these yeasts, which could be dependent on specific and non-conserved domains present in these two proteins.
Highlights
Accepted: 16 September 2021Easy manipulation and availability of high throughput platforms to evaluate the response of yeast cells to directed mutations and drugs strengthen the rationale of using these organisms as disease models, or for testing chemical libraries to find new therapeutic treatments [1,2,3]
The results show that deletion of KlIXR1 does not increase cisplatin resistance as reported for the ScIXR1 gene deletion in S. cerevisiae [27], but oppositely, the cytotoxic effect of the drug was increased in the MW190-9b-ixr1∆ null mutant (Figure 3a)
The results show that KlIxr1 depletion downregulates the KlSFP1 gene, the repressor KlCRF1 gene is upregulated (Figure 3c), indicating that KlIxr1 regulation exerted on ribosome synthesis processes through these two regulators in K. lactis is identical to that observed previously in S. cerevisiae [29]
Summary
Accepted: 16 September 2021Easy manipulation and availability of high throughput platforms to evaluate the response of yeast cells to directed mutations and drugs strengthen the rationale of using these organisms as disease models, or for testing chemical libraries to find new therapeutic treatments [1,2,3]. Have been traditionally used with this purpose or as cell factories, but there are many other yeasts that could be included as far as the knowledge of their biology and regulatory molecular mechanisms controlling principal functions would increase. The HMGB protein family is characterized for presenting one or more HMG-box domains with DNA/RNA binding abilities. In multicellular eukaryotes, these proteins are implicated in many DNA-dependent nuclear processes at the chromatin level [6]. (sequence and non-sequence specific), and in the cytoplasm [7], or extracellularly acting in cell signaling and inflammation [8]. In the nucleus HMGB proteins from yeast and other higher eukaryotes are functionally involved in chromatin interactions, DNA repair, transcriptional regulation, and epigenetic control of gene expression. Cytoplasmic functions of HMGB proteins, like human HMGB1, are related to the balance between
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