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Biomedical subjects

G Dujardin

Publications and source records attributed to G Dujardin.

61 records · Page 4Linked to original sources
PubMed1982

Single base substitution in an intron of oxidase gene compensates splicing defects of the cytochrome b gene.

An extragenic suppressor mutation, mim2-1, which compensates yeast mitochondrial mutants deficient in splicing of the cytochrome b gene, has been mapped and sequenced. The mutation is due to a single G leads to A transition in the long open reading frame of the fourth intron of the oxidase subunit one gene. It causes the replacement of a glutamic codon by a lysine codon and the expression of a novel mRNA maturase active in splicing. Evolution and regulatory connections between homologous introns of nonhomologous genes are discussed.

Base Sequence↗
PubMed1981

Long range control circuits within mitochondria and between nucleus and mitochondria. II. Genetic and biochemical analyses of suppressors which selectively alleviate the mitochondrial intron mutations.

In the preceding paper of this series (Dujardin et al. 1980 a) we described general methods of selecting and genetically characterizing suppressor mutations that restore the respiratory capacity of mit- mitochondrial mutations. Two dominant nuclear (NAM1-1 and NAM2-1) and one mitochondrial (mim2-1) suppressors are more extensively studied in this paper. We have analysed the action spectrum of these suppressors on 433 mit- mutations located in various mitochondrial genes and found that they preferentially alleviate the effects of mutations located within intron open reading frames of the cob-box gene. We conclude that these suppressors permit the maturation of cytochrome b mRNA by restoring the synthesis of intron encoded protein(s) catalytically involved in splicing i.e. mRNA-maturase(s) (cf. Lazowska et al. 1980). NAM1-1 is allele specific and gene non-specific; it suppresses mutations located within different introns. NAM2-1 and mim2-1 are intron-specific: they suppress mutations all located in the same (box7) intron of the cob-box gene. Analyses of cytochrome absorption spectra and mitochondrial translation products of cells in which the suppressors are associated with various other mit- mutations show that the suppressors restore cytochrome b and/or cytochrome oxidase (cox I) synthesis, as expected from their growth phenotype. This suppression is, however, only partial: some new polypeptides characteristic of the mit- mutations can be still detected in the presence of suppressor. Interestingly enough when box7 specific suppressors NAM2-1 and mim2-1 are associated with a complete cob-box deletion (leading to a total deficiency of cytochrome b and oxidase) partial restoration of cox I synthesis is observed while cytochrome b is still totally absent. These results show that in strains carrying NAM2-1 or mim2-1 the presence of cytochrome b gene is no longer required for the expression of the oxi3 gene pointing out to the possibility of a mutational switch-on of silent genes, whether mitochondrial, mim2-1, or nuclear, NAM2-1. This switch-on would permit the synthesis of an active maturase acting as a substitute for the box7 maturase in order to splice the cytochrome b and oxidase mRNAs.

Base Sequence↗
PubMed1980

Long range control circuits within mitochondria and between nucleus and mitochondria. I. Methodology and phenomenology of suppressors.

To uncover the functional circuitry both within the mitochondrial genome and between the mitochondrial and the nuclear genome, we have developed a general method for selecting and characterizing genetically suppressor mutations that restore the respiratory capacity of mit- mitochondrial mutants. Several hundreds of pseudo-wild type revertants due to a second unlinked mutation which suppresses a target mit- mutation were isolated. The suppressor mutations were found located either in the nuclear (abbreviated NAM for 'nuclear accommodation of mitochondria') or in the mitochondrial genome (abbreviated MIM for 'mitochondrial-mitochondrial interaction'). The specificity of action of various suppressors upon some 250 different mit- mutations located in several genes was tested. According to this specificity of action, suppressors were subdivided into two major classes: allele specific or gene specific suppressors. Because the cob-box mitochondrial gene has a mosaic organization, we were able to find a novel third class of extragenic suppressors specific for mit- mutations within the introns of this gene. Four examples of suppressors showing various specificities of action illustrate our approach. (1) a nuclear gene controlling specific alleles of different mitochondrial genes; (2) a nuclear gene controlling selectively one intron of a split mitochondrial gene; (3) a mitochondrial gene controlling specific alleles of different mitochondrial genes; (4) a region in one complex mitochondrial gene which controls selectively one intron of another split mitochondrial gene. Different mechanisms of suppression are discussed stressing the alleviation of splicing deficiencies of intron mutations.

Clone Cells↗
PubMed1979

Mutants in yeast affecting ethidium bromide induced rho- formation and their effects on transmission and recombination of mitochondrial genes.

A series of mutants called ebi, less inducible by ethidium bromide than the parental strain for the rho+ leads to rho- mutation have been isolated after E.M.S. mutagenesis. Some of the ebi mutants also show an important accumulation of rho- cells, in the absence of ethidium bromide. Ebi mutations are nuclearly inherited as shown by meiotic segregation. The effects of these mutants on the transmission and recombination of mitochondrial genes among the diploid progeny of crosses have been studied. Some of the ebi mutants show a non coordinated transmission of the oli1 mitochondrial marker with respect to other mitochondrial markers unexpected for homosexual crosses. This bias which is independent from omega will be discussed in relation to the segregation and recombination. No significant decrease of the frequency of recombinants has been detected.

Crosses, Genetic↗
PubMed1979

Petite deletion map of the mitochondrial oxi3 region in Saccharomyces cerevisiae.

Fifty eight mitochondrial mutants (p + mit- mutants), all deficient in cytochrome oxidase activity and previously assigned to the genetic region oxi3 on the mitochondrial DNA, were mapped by the method of "petite deletion mapping". This procedure resulted in the identification of at least twenty one different classes of oxi3 mutants, which could be arranged in a linear order. Moreover, it provided a set of twenty three p- petite mutants, each containing a differentially deleted mit DNA segment included in the oxi3 region. The two sets of mutants, p+ oxi3- and p- oxi3+, will be of interest for a further genetic and physical analysis of this mitochondrial DNA segment which spans over about ten thousand base pairs and controls the subunit I of cytochrome oxidase.

DNA, Mitochondrial↗