Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.9.3.1 (cytochrome oxidase)
 8,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Yeast cells carrying a mutation in the OXA1 nuclear gene are respiratory deficient and lack cytochrome oxidase activity. We successively examined the different steps in the expression of the mitochondrial genes encoding the cytochrome oxidase subunits and apocytochrome b in strains carrying the oxa1-79 mutation. The ox1-79 strains exhibit a total absence of cytochrome aa3 and a decrease in cytochrome b, even in a strain devoid of mitochondrial introns, in which cox1 and cytb mRNAs normally accumulate. The three mitochondrial-encoded subunits of cytochrome oxidase are still detectable although their amount is reduced, and apocytochrome b is synthesized normally. These results suggest that the OXA1 gene is primary required at a post-translational step in cytochrome oxidase biogenesis, probably at the level of assembly, although the oxa1-79 mutation leads to some pleiotropic secondary defects in earlier steps of mitochondrial gene expression. The OXA1 gene has been cloned, sequenced, and disrupted. The phenotypes of the oxa1::LEU2 and oxa1-79 alleles are similar. Interestingly, the OXA1 gene, located on the yeast chromosome VIII, is adjacent to the gene PET 122, which controls the initiation of cox3 mRNA translation. In addition, the predicted OXA1 protein is homologous to several putative prokaryotic and eukaryotic proteins, suggesting that the function of the OXA1 protein is important for respiration in all living cells.
 ...
PMID:OXA1, a Saccharomyces cerevisiae nuclear gene whose sequence is conserved from prokaryotes to eukaryotes controls cytochrome oxidase biogenesis. 819 54

The antitumor activity of bleomycin is associated with its ability to produce DNA lesions. The cellular process that repairs bleomycin-induced DNA lesions is not entirely clear. To understand how these DNA lesions are repaired in eukaryotic cells, we used mini Tn3 : : LEU2 :: LacZ transposon mutagenesis to isolate yeast mutants that were hypersensitive to bleomycin. One of the mutants, HCY69, was characterized further and found to be 4- and 3-fold more sensitive, respectively, to bleomycin and hydrogen peroxide, as compared to the parent. The mutant displayed parental resistance to a variety of other DNA-damaging agents. Plasmid rescue and DNA sequence analysis revealed that the transposon interrupted the OXA1 gene, which encodes a protein required to process one of the subunits, cox II, of the cytochrome oxidase complex in mitochondria. A plasmid carrying the native OXA1 gene fully restored drug resistance to strain HCY69. Our data strongly suggest that functional mitochondria are required for cellular protection against the toxic effects of bleomycin.
 ...
PMID:Functional mitochondria are essential for Saccharomyces cerevisiae cellular resistance to bleomycin. 878 Nov 69