Gal 32 is a Chinese hamster lung (CHL) cell mutant that is unable to grow in galactose due to a defect in mitochondrial (mt) protein synthesis, perhaps at the level of excision of tRNA sequences from the polycistronic mt transcripts. A single, nuclear recessive mutations is responsible for the differential reduction in mt synthesized proteins. This laboratory has isolated two recombinant cosmid clones containing a human gene that complements the Chinese hamster Gal 32 mutation. Since the genomic insert is very large, the minimal size of the human gene will be ascertained by combining restriction enzyme analysis and gene transfer into Gal 32 cells. Northern blotting will be utilized to determine the number and sizes of RNAs hybridizing to the human gene and tissue specific expression. A cDNA clone for the human gene will isolated from a human heart cDNA library. The genomic and cDNA clones will be sequenced. The regulatory regions in the genomic clone will be investigated using deletions, mutagenesis, DNA footprinting, and mobility shift DNA binding assays. The function of the protein will be explored by comparison of the cDNA sequence to the data banks, and examining the sizes of mt tRNAs in wild type and mutant cells. Structure-function of the protein will be investigated using site-directed mutagenesis. The gene will be mapped to a human chromosome by Southern blotting of human/rodent hybrid cell DNA. These studies will elucidate the structure, regulation, tissue specificity, and product of the human gene and will contribute to our understanding of mt gene expression.

Project Start
Project End
Budget Start
Budget End
Support Year
26
Fiscal Year
1996
Total Cost
Indirect Cost
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