Sup35 prionization [PSI+] influence the frequency of the gene and chromosome mutations, accounted in the alpha-test in yeast Saccharomyces cerevisiae

Abstract

Background. A lot of neurodegenerative diseases are coursed by amiloidization of proteins in nerve tissues. In the patients brains suffered from Alzheimer’s disease the high fraction of the nerve cells with abnormal chromosome amount was revealed. There are some data showing that prion form of protein PrP may prevent chromosome segregation in mitosis. But the direct association of prionisation and genome stability was not revealed. Materials and methods. We compared the yeast S. cerevisiae strain bearing the prion form of the termination translation factor Sup35, and the strain with non-prionized Sup35 in the alpha-test system. The model of the alpha-test is based on the mechanism of mating type switching in heterothallic yeast strains. The MAT locus that controls the mating type of yeast cell can be presented by two idiomorphs: the MATalpha and MATa that determine the alpha and a cell types, correspondingly. Only two cells with opposite mating types (alpha × a) could copulate. In the mixture of two yeast strains with alpha mating type the hybrids appears only if one of the parent cells had changed its mating type alpha → a. The mating type switching could course the following genetic events: the loss of the chromosome, gene conversion, recombination, loss of the arm of the chromosome, gene mutations and temporary lesions. These events could be distinguished by using the specially constructed alpha-test system. Results. The [PSI+] strain has showed 2-times decreased frequency of «illegitimate» hybridization in the alpha-test compared to [psi-] strain. But [PSI+] doesn’t influence the frequency of «legitimate» hybridization in the alpha × a crossing. The prion [PSI+] also 2-times reduces the frequency of chromosome loss and gene mutations and increases gene conversion 5-times. This results are also confirmed by the canavanine test. Conclusion. We investigated the effect of the Sup35 prionizaion on the genome stability. Unexpectedly in the [PSI+] strain the frequency of «illegitimate» hybridization was 2-times lower, and frequency of gene mutations and chromosome loss was also reduced. The mechanism of this effect is unclear and requires the further investigation.