[HSM6 gene is identical to PSY4 gene in Saccharomyces cerevisiae yeasts].

Previously, we isolated mutant yeasts Saccharomyces cerevisiae with an increased rate of spontaneous mutagenesis. Here, we studied the properties of HSM6 gene, the hsm6-1 mutation of which increased the frequency of UV-induced mutagenesis and decreased the level of UV-induced mitotic crossover at the centromere gene region, ADE2. HSM6 gene was mapped on the left arm of chromosome 11 in the region where the PSY4 gene is located.

[Interaction of the HSM3 gene with genes initiating homologous recombination repair in yeast Saccharomyces cerevisiae].

It was assumed previously that the mutator phenotype of the hms3 mutant was determined by processes taking place in the D-loop. As a next step, genetic analysis was performed to study the interactions between the hsm3 mutation and mutations of the genes that control the initial steps of the D-loop formation. The mutations of the MMS4 and XRS2 genes, which initiate the double-strand break formation and subsequent repair, were shown to completely block HSM3-dependent UV-induced mutagenesis.

[Interaction of gene HSM3 with genes of the epistatic RAD6 group in yeast Saccharomyces cerevisiae].

In eukaryotes, damage tolerance of matrix DNA is mainly determined by the repair pathway under the control of the RAD6 epistatic group of genes. T this pathway is also a main source of mutations generated by mutagenic factors. The results of our recent studies show that gene HSM3 participating in the control of adaptive mutagenesis increases the frequency of mutations induced by different mutagens.

[IXR1 and HMO1 genes jointly control the level of spontaneous mutagenesis in yeast Saccharomyces cerevisiae].

The yeast genes IXR1 and HMO1 encode proteins belonging to the family of chromatin nonhistone proteins, which are able to recognize and bind to irregular DNA structures. The full deletion of gene IXR1 leads to an increase in cell resistance to the lethal action of UV light, gamma-rays, and MMS, increases spontaneous mutagenesis and significantlly decreases the level of UV-induced mutations. It was earlier demonstrated in our works that the hmo 1 mutation renders cells sensitive to the lethal action of cisplatin and virtually does not affect the sensitivity to UV light.

[Genetic analysis of the Hsm3 protein domain structure in yeast Saccharomyces cerevisiae].

Gene HSM3 encodes the Hsm3 protein involved in the minor branch in the system responsible for the correction of mismatched bases in DNA structure and controls replicative and reparative spontaneous mutagenesis in yeast Saccharomyces cerevisiae. Spontaneous and UV-induced mutagenesis was studied in three mutant alleles of gene HSM3, and repair effectivity of artificial heteroduplexes was assessed in DNA molecule. The resuts of these studies allowed establishment of the protein domain structure of protein Hsm3 and functions of each domain: the N-terminal domain is responsible for binding to mispaired bases, and the C-terminal domain ensures the interaction with other proteins involved in the system of mismatched base correction.

[The geptrong pharmaceutical product increases efficiency of postreplication repair of permutation intermediates in yeast Saccharomyces cerevisiae].

Geptrong is a medication from pure defermentated honey. In medical practice, it is used as hepatoprotector. Genotoxicity analysis revealed antimutagenic activity of the preparation.

[Repair of cisplatin-DNA adducts in mutants for genes controlling spontaneous and induced mutagenesis in Saccharomyces cerevisiae].

Sensitivity to the lethal action of the anticancer substance cisplatin was studied in the yeast mutants himl, hsm2, hsm3, and hsm6, deficient for repair of spontaneous and induced mutations. The himl and hsm3 mutants were as resistant to the agent under study as the wild-type strain. The survival of the double mutant rad2 hsm3 was higher than that of the single mutant rad2.

[Mutator genes of the yeast Saccharomyces cerevisiae. Interaction of mutations him and his with mutations blocking three principal pathways of repair of induced DNA damage].

During recent years, genes controlling mutation in higher eukaryotes have been found to be involved actively in carcinoma regeneration in cells. In this respect, studying the genetic control of mutagenesis becomes a key direction of research into mechanisms responsible for cancer generation. The results of studying interaction of mutations in the HIM and HSM genes, controlling spontaneous and induced mutagenesis in yeasts, and mutations impairing three known pathways of DNA damage repair in this microorganism, are described in this work.

[Mutator genes from Saccharomyces cerevisiae. Interaction between HIM- and HSM-genes].

The interaction of six mutator genes of the yeast Saccharomyces cerevisiae with respect to UV-induced mutagenesis was studied. To this effect, double mutants with a genotype containing pairs of mutations at genes analyzed were synthesized. Analysis of the type of interaction of these mutations revealed four epistatic gene groups: (1) HIM1, HSM3, and HSM6; (2) HSM1; (3) HSM2; and (4) HIM2 and HIM3.

[Mutator genes from Saccharomyces cerevisiae. Repair of artificial heteroduplexes in him and hsm mutants].

During recent years, genes controlling mutation in higher eukaryotes have been found to be involved actively in carcinoma regeneration in cells. In this respect, studying the genetic control of mutagenesis becomes a key direction of research into mechanisms responsible for cancer generation. The results of studying interaction of mutations in the HSM3 and HSM6 genes, controlling spontaneous and induced mutagenesis in yeasts, and mutations impairing three known pathways of DNA damage repair in this microorganism, are described in this work.

[A strain of the yeast Saccharomyces cerevisiae for testing environmental mutagens based on interaction of the mutations rad2 and him1].

The interaction between mutations at the RAD2 and HIM1 genes was studied. The RAD2 gene encodes endonuclease involved in nucleotide excision repair. Mutants at this gene are highly sensitive to the lethal effect of a variety of mutagens.

[Effect of hms mutations increasing spontaneous mutability on induced mutagenesis and mitotic recombination in the yeast Saccharomyces cerevisiae].

The influence of five nonallelic mutations hsm-1-hsm-5 on the frequency of mutations induced by UV-light, 6-hydroxyl-aminopurine (GAP) and nitrosomethylurea (NMM) at the ADE1 and ADE2 loci was studied. All hsm mutants were resistant to the lethal effect of these mutagens. The frequency of mutations induced by UV-light was increased in hsm2-1, hsm3-1, hsm5-1 and especially in hsm1-1 mutants, the hsm4-1 mutant not differing from the HSM strain.

[Participation of the HIM1 gene from Saccharomyces cerevisiae in correction of heteroduplex DNA. Molecular cloning of the gene].

A group of Saccharomyces cerevisiae mutants deficient in repair of induced premutation lesions (him mutants) were previously isolated in our laboratory. Recessive him1 mutant had enhanced level of spontaneous and induced mutagenesis as well as specific altered mitotic conversion. This HIM1 gene was supposed to be involved in the process of mismatch correction of heteroduplexes.

[Isolation and characteristics of new mutants of Saccharomyces cerevisiae with increased spontaneous mutability].

To isolate some new genes controlling the process of spontaneous mutagenesis, a collection of 16 yeast strains with enhanced rate of spontaneous canavanine resistant mutations was obtained. Genetical analysis allowed to define that the mutator phenotype of these strains is due to a single nuclear mutation. Such mutations were called hsm (high spontaneous mutagenesis).

[Mapping the xrs2 and him1 genes of Saccharomyces cerevisiae by a method based on the chromosome destabilization effect].

The methods for chimeric chromosomes' destabilization and the standard tetrad analysis have been used for mapping of the yeast genes XRS2 and HIM1. The genes are localized in the right arm of chromosome IV in the following order: XRS2-31cM-ADE8-28.5cM-HIM1.

[The effect of him mutations characterized by enhanced induced mutagenesis on the spontaneous mitotic recombination in the ADE2 gene in Saccharomyces cerevisiae].

We have studied the influence of him1, him2, him3 and himX mutations on the frequency of spontaneous mitotic gene conversion in the yeast Saccharomyces cerevisiae using the set of heteroallelic combinations in the ADE2 gene. Data obtained on the HIM/HIM, him/him homozygotes and HIM/him heterozygotes indicate that the him1 mutation is recessive with respect to conversion, whereas the him2, him3 and himX mutations are semidominant. Gene conversion was increased in the majority of heteroalleles of mutant diploids him1/him1.

[Mutants of the yeast Saccharomyces cerevisiae characterized by enhanced induced mutagenesis. III. Effect of the him mutation on the effectiveness and specificity of UF-induced mutagenesis].

We have studied the influence of him1-1, him2-1, him3-1 and himX mutations on induction frequency and specificity of UV-induced adenine-dependent mutations in the yeast Saccharomyces cerevisiae. Him mutations do not render haploid cells more sensitive to the lethal action of UV-light; however, in him strains adenine-dependent mutations (ade1, ade2) were induced more frequently (1.5--2-fold), as compared to the HIM strain.

[Saccharomyces cerevisiae mutants characterized by increased induced mutagenesis. II. Genetic analysis of mutants].

Induction of forward adenine-dependent (Ade+----Ade-) mutations by HAP was used to analyse genetically yeast mutants with enhanced induced mutagenesis. Three mutations studied in detail segregated as a single mendelian trait and composed independent complementation groups (HIM1, HIM2, HIM3). the him1-1 mutation was centromere-linked, the him3-1 and him2-1 mutations being not.

[Mutants of Saccharomyces cerevisiae characterized by increased level of induced mutagenesis. I. Isolation and preliminary characterization of mutants].

6 mutants with enhanced nitrous acid-induced reversibility of the ade2-42 allele were isolated and designated hm (high mutagenesis). Apart from sensitivity to the mutagenic exposure to nitrous acid, hm mutants were also spontaneous mutators and hypermutable under the action of UV-light and 6-N-hydroxyaminopurine. All these effects were detected not only when analysing reversibility of the ade2-42 allele, but also when scoring forward mutations in the ADE1, ADF2 genes.

[Molecular nature of direct gene mutations induced by gamma and ultraviolet irradiation in Saccharomyces cerevisiae yeasts].

The spectrum of gamma- and UV-induced mutations for ADE2 locus of the yeast Saccharomyces cerevisiae was determined as follows (respectively): 27 and 41% GC leads to AT transitions, 8 and 11% AT leads to GC transitions, 59 and 40% transversions, 6 and 8% frameshifts. Our results indicate a specificity of UV-light for GC leads to AT transitions. Experimental data are discussed in a view of molecular mechanisms of radiation mutagenesis.

[Intragenic mitotic recombination induced by ultraviolet and gamma rays in radiosensitive mutants of Saccharomyces cerevisiae yeasts].

The effect of UV- and gamma-irradiation on the survival and intragenic mitotic recombination (gene conversion) of 5 radiosensitive mutants was studied in comparison with the wild type. The level of spontaneous conversion was similar for RAD, rad2 and rad15, mutations xrs2 and xrs4 increasing and rad54 significantly decreasing it. The frequency of conversion induced by UV-light was greater in rad2, rad15 and xrs2 mutants and lower in xrs4, as compared to RAD.

A new mutant of the yeast Saccharomyces cerevisiae defective in excision of UV-damaged sites in DNA.

An UV-sensitive yeast mutant, uvs12, with almost unchanged sensitivity to gamma-irradiation and methylmethane sulphonate was obtained. uvs12, non allelic to any of the known UV-sensitive mutants from radI to rad21 is defective in early steps of excision repair. This inference is based on the fact that after 4-5 h post-irradiation incubation unexcised pyrimidine dimers are retained in nuclear DNA, which follows from two independent tests: the retention of UV-endonuclease-sensitive sites and enhanced survival after photoreactivation.

[Genetic effects of N-nitroso-N-methylurea on Saccharomyces cerevisiae yeasts. I. The influence of radiosensitivity mutations on lethal and recombinogenic effects].

Effect of mutations rad2 and rad54 in homozygous state on survival, mitotic segregation and crossing-over induced by NMU in yeast was studied. Mutation rad2 did not influence on these effects of NMU. The mutation rad54 increased sensitivity to the lethal effect, the frequencies of NMU-induced segregation and crossing-over were decreased in the strain rad54 rad54.