Thiol peroxidase deficiency leads to ıncreased mutational load and decreased fitness in saccharomyces cerevisiae
Yükleniyor...
Dosyalar
Tarih
2014
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Genetics
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
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.
Açıklama
Genetics, Vol. 198, 905–917 November 2014
Anahtar Kelimeler
Kaynak
Genetics
WoS Q Değeri
Scopus Q Değeri
Cilt
198
Sayı
0
Künye
Kaya A, Lobanov AV, Gerashchenko MV, Koren A, Fomenko DE, Koc A, Gladyshev VN. (2014). Thiol peroxidase deficiency leads to ıncreased mutational load and decreased fitness in saccharomyces cerevisiae. Genetics, Vol. 198, 905–917.
