The molecular biological approach to the study of the mitochondrial genetic code and the regulation of expression of mitochondrial genes will include the following specific investigations directed at the yeast genes oxi-1 and oxi-2, which code for cytochrome oxidase subunits II and III: a) DNA sequence analysis of mutations in these genes, already in hand, including those that cause premature polypeptide chain termination in vivo. Mutations generating codons not normally used in yeast mitochondrial genes may be identified. The information will be further applied to the further study of suppressor mutations in the mitochondria. b) The isolation and characterization of spontaneous mutations in these mitochondrial genes. This information will have evolutionary significance and eventually serve as a basis for the detailed study of specific effects of mutagens on mitochondrial DNA. c) Development of a system for the genetic transformation of yeast mitochondria to study the movement of genes within the cell. d) Detailed characterization of the transcripts copied from the oxi-1 and oxi-2 genes, both in wild-type and mutant strains. The effect of changes in the physiological growth conditions on mitochondrial transcription will also be examined. e) A study of the mechanisms by which three previously described nuclear genes regulate the expression of the oxi-1 and oxi-2 genes, by examining their effects on mitochondrial transcription and by cloning the nuclear genes themselves. These studies will bear on the evolution of organelle systems in eucaryotic cells, and on the intracellular coordination of distinct genetic systems. These questions can be studied in the greatest depth with the well developed genetic system of yeast.

Project Start
1983-07-01
Project End
1988-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
3
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Cornell University
Department
Type
Schools of Arts and Sciences
DUNS #
City
Ithaca
State
NY
Country
United States
Zip Code
14850
Costanzo, M C; Seaver, E C; Fox, T D (1989) The PET54 gene of Saccharomyces cerevisiae: characterization of a nuclear gene encoding a mitochondrial translational activator and subcellular localization of its product. Genetics 122:297-305
Marykwas, D L; Fox, T D (1989) Control of the Saccharomyces cerevisiae regulatory gene PET494: transcriptional repression by glucose and translational induction by oxygen. Mol Cell Biol 9:484-91
Fox, T D; Sanford, J C; McMullin, T W (1988) Plasmids can stably transform yeast mitochondria lacking endogenous mtDNA. Proc Natl Acad Sci U S A 85:7288-92
Costanzo, M C; Fox, T D (1988) Transformation of yeast by agitation with glass beads. Genetics 120:667-70
Costanzo, M C; Fox, T D (1988) Specific translational activation by nuclear gene products occurs in the 5' untranslated leader of a yeast mitochondrial mRNA. Proc Natl Acad Sci U S A 85:2677-81
Strick, C A; Fox, T D (1987) Saccharomyces cerevisiae positive regulatory gene PET111 encodes a mitochondrial protein that is translated from an mRNA with a long 5' leader. Mol Cell Biol 7:2728-34
Fox, T D (1987) Natural variation in the genetic code. Annu Rev Genet 21:67-91
Poutre, C G; Fox, T D (1987) PET111, a Saccharomyces cerevisiae nuclear gene required for translation of the mitochondrial mRNA encoding cytochrome c oxidase subunit II. Genetics 115:637-47
Rodel, G; Fox, T D (1987) The yeast nuclear gene CBS1 is required for translation of mitochondrial mRNAs bearing the cob 5' untranslated leader. Mol Gen Genet 206:45-50
Costanzo, M C; Mueller, P P; Strick, C A et al. (1986) Primary structure of wild-type and mutant alleles of the PET494 gene of Saccharomyces cerevisiae. Mol Gen Genet 202:294-301

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