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Title: Thiol peroxidase deficiency leads to increased mutational load and decreased fitness in saccharomyces cerevisiae
Authors: Kaya, Alaattin
Lobanov, Alexey V.
Gerashchenko, Maxim V.
Koren, Amnon
Fomenko, Dmitri E.
Koç, Ahmet
Gladyshev, Vadim N.
Keywords: Fungal DNA
Fungal enzyme
Genomic DNA
Saccharomyces cerevisiae
Thiol peroxidase
Issue Date: Nov-2014
Publisher: Genetics Society of America
Source: Kaya, A., Lobanov, A.V., Gerashchenko, M.V., Koren, A., Fomenko, D.E., Koç, A., and Gladyshev, V.N. (2014). Thiol peroxidase deficiency leads to increased mutational load and decreased fitness in saccharomyces cerevisiae. Genetics, 198(3), 905-917. doi:10.1534/genetics.114.169243
Abstract: Thiol peroxidases are critical enzymes in the redox control of cellular processes that function by reducing low levels of hydroperoxides and regulating redox signaling. These proteins were also shown to regulate genome stability, but how their dysfunction affects the actual mutations in the genome is not known. Saccharomyces cerevisiae has eight thiol peroxidases of glutathione peroxidase and peroxiredoxin families, and the mutant lacking all these genes (Δ8) is viable. In this study, we employed two independent Δ8 isolates to analyze the genome-wide mutation spectrum that results from deficiency in these enzymes. Deletion of these genes was accompanied by a dramatic increase in point mutations, many of which clustered in close proximity and scattered throughout the genome, suggesting strong mutational bias. We further subjected multiple lines of wild-type and Δ8 cells to long-term mutation accumulation, followed by genome sequencing and phenotypic characterization. Δ8 lines showed a significant increase in nonrecurrent point mutations and indels. The original Δ8 cells exhibited reduced growth rate and decreased life span, which were further reduced in all Δ8 mutation accumulation lines. Although the mutation spectrum of the two independent isolates was different, similar patterns of gene expression were observed, suggesting the direct contribution of thiol peroxidases to the observed phenotypes. Expression of a single thiol peroxidase could partially restore the growth phenotype of Δ8 cells. This study shows how deficiency in nonessential, yet critical and conserved oxidoreductase function, leads to increased mutational load and decreased fitness.
ISSN: 0016-6731
Appears in Collections:Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik
PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection

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