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Biomedical subjects

M Brendel

Publications and source records attributed to M Brendel.

126 records · Page 7Linked to original sources
PubMedDate not supplied

Molecular characterisation of GTP1, a Saccharomyces cerevisiae gene encoding a small GTP-binding protein.

DNA sequence analysis upstream of the yeast DNA repair gene SNM1 revealed gene GTP1 with an ORF of 573 bp on chromosome XIII. The putative amino-acid sequence of the encoded protein shows homology to proteins of the ARF-class of small GTP-binding proteins. Homology within GTP-binding motifs is highly conserved. Gene disruption showed that GTP1 is not an essential gene and that it has no influence on the expression of the DNA repair gene SNM1 with which it shares a 191-bp promoter region.

ADP-Ribosylation Factors↗
PubMedDate not supplied

DNA alkylation by mustard gas in yeast strains of different repair capacity.

Reaction of the toxic and mutagenic alkylating agent mustard gas with DNA of the yeast Saccharomyces cerevisiae was analyzed qualitatively and quantitatively. Within the dose range tested (2 X 10(-5)-2 X 10(-3) M) DNA in vivo is alkylated dose-proportionally. DNA alkylation and relative distribution of purine derivatives are not influenced by the cell's sensitivity towards the mutagen. At LD37 (4.4 X 10(-4) M) the wild type contains 44 300 purine derivatives: 9200 3-alkyladenines (20%), 29600 7-alkylguanines (67%) and 5500 diguaninyl derivates (13%) per genome. In sensitive strains the number of derivates per genome at LD37 is reduced according to the dose reduction factor. Alkylation at the position O6 of guanine by mustard gas cannot be shown, the method's limit of detection being 0.3% amongst purine derivates.

Alkylation↗
PubMedDate not supplied

Genotoxicity of excess thymidylate in thymidylate low-requiring Saccharomyces cerevisiae is associated with changes in phosphate metabolism.

When dTMP in concentrations greater than 100 microM is offered to growing cells of thymidylate low-requiring yeast strains it is both mutagenic and toxic. At exposure concentrations greater than 1 mM dTMP interferes significantly with the low-affinity phosphate permease even in the presence of exogenous phosphate concentrations of 6 mM. Chemical analysis and 31P NMR spectroscopy reveal that excess dTMP disturbs phosphate metabolism in thymidylate low-requiring strains but not in the wild type. The most prominent changes in phosphorus-containing molecules are found in polyphosphates of which up to 20% are broken down within a 20-min time span with a concomitant increase in orthophosphate pools.

Biological Transport↗
PubMedDate not supplied

UV-induction of thymine-containing dimers in Saccharomyces cerevisiae.

In haploid and diploid S. cerevisiae the dimer yield ratio TT/CT is found to be 1.2/1 and 1.3/1, resp., at the UV (254 nm) unit dose 1 erg/mm2, the share of TT and CT in a UV (254 nm) lethal hit being 0.7 TT and 0.6 CT. A general formulation of the UV lethal hit is given and discussed. The TT+CT yields obtained for S. cerevisiae are compared to those reported for other organisms. It is found that there obviously exists a directly proportional linear correlation between genome size and TT+CT yield for the UV dose range well below the stationary levels of the TT and CT formation kinetics.

DNA↗
PubMedDate not supplied

Isolation and properties of yeast mutants with highly efficient thymidylate utilization.

A screening procedure is presented which allows the isolation of yeast mutants (typ tir) with highly efficient utilization of exogenous deoxythymidine-5'-monophosphate (5'-dTMP) (greater than 50%). Data are given concerning the phenomenon of 5'-dTMP utilization in general: (i) The ability of S. cerevisiae to incorporate exogenous 5'-dTMP was found to already to be a wild type feature of this yeast, i.e. apparently not to be due to any mutation such as typ, tup, tmp, per or tum. Consequently these mutations are interpreted as amplifiers of a pre-given wild type potency. So far eight stages of 5'-dTMP utilization were detected as classified by the optimal 5'-dTMP requirement, with 5'-dTMP biosynthesis blocked, of the corresponding mutant strains isolated. All of them fit well into a mathematical series of the type "2n x 1.5" (n = 0, 1, 2, ..., 11), where the product term for n = 11 represents the 5'-dTMP requirement (mug/ml) of the best 5'-dTMP utilizing wild type strain found. (ii) Amplification of the 5'-dTMP utilizing potency obviously is due to any genetically determined alteration of the yeast 5'-dTMP uptaking principle itself or of physiological processes accompanying the monophosphate's uptake. (iii) The functioning of 5'-dTMP uptake requires acidic (less than or equal to pH 6) conditions in the yeast cell's outer environment. (iv) Some yeast typ and typ tlr mutants were found to exhibit a more or less pronounced sensitivity towards exogenously offered 5'-dTMP. The response of a sensitive strain towards inhibitory concentrations of the nucleotide apparently is co-conditioned by the presence or absence of thymidylate biosynthesis. With 5'-dTMP biosynthesis blocked the 5'-dTMP mediated inhibition is a permanent one and finally leads to the death of a cell. With a functioning thymidylate biosynthesis, in contrast, the inhibition is only temporary. (v) Yeast typ or typ tlr strains were observed to dephosphorylate exogenous 5'-dTMP to thymidine due to a phosphatase activity which cannot be eliminated at pH 7 + 70 mM inorganic phosphate conditions in the growth medium. This 5'-dTMP cleavage obviously occurs outside the cell and does not seem to be correlated both to the monophosphate's uptake and to the phenomenon of 5'-dTMP sensitivity. The destruction of 5'-dTMP does not disturb (5'-dTMP) DNA-specific labelling.

Genes↗