Abstract

The long-term goal of this proposal is to understand the control of mtDNA copy number in mammals and hence regulation of intracellular mitochondrial activity and patterns of mitochondrial gene transmission. Using tissue from an evolutionarily related set of artiodactyl species, our approach will focus on three molecular levels of mitochondrial function. (1) Light strand (L-strand) transcripts prime heavy-strand (H-strand) DNA synthesis. the initial event in mtdNA replication. Therefore the role which sequences upstream of L-strand transcript 5' ends play in determining the accuracy and efficiency of transcription will be determined. (2) H-strand synthesis initiates downstream of the L- strand promoter and usually terminates abortively near sequences will conserved in all mammals, thereby creating triple-stranded D- loop DNA. Therefore cis and trans-elements which regulate initiation and termination of D-loop DNA synthesis will be determined. (3) The generation and segregation of heteroplasmic mitochondria in mammalian tissue are related to developmental changes in mtDNA copy number. Therefore the developmental and generation-to-generation fate of heteroplasmic mtDNA in a unique maternal lineage of Holstein cows will be measured to provide a link between the control of mtDNA replication and mitochondrial transmission genetics.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM034825-04
Application #
3286483
Study Section
Physiological Chemistry Study Section (PC)
Project Start
1985-09-01
Project End
1993-08-31
Budget Start
1988-09-01
Budget End
1989-08-31
Support Year
4
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
University of Florida
Department
Type
Schools of Medicine
DUNS #
073130411
City
Gainesville
State
FL
Country
United States
Zip Code
32611

  Publications

Ghivizzani, S C; Madsen, C S; Nelen, M R et al. (1994) In organello footprint analysis of human mitochondrial DNA: human mitochondrial transcription factor A interactions at the origin of replication. Mol Cell Biol 14:7717-30
Ghivizzani, S C; Madsen, C S; Hauswirth, W W (1993) In organello footprinting. Analysis of protein binding at regulatory regions in bovine mitochondrial DNA. J Biol Chem 268:8675-82
Madsen, C S; Ghivizzani, S C; Hauswirth, W W (1993) Protein binding to a single termination-associated sequence in the mitochondrial DNA D-loop region. Mol Cell Biol 13:2162-71
Madsen, C S; Ghivizzani, S C; Hauswirth, W W (1993) In vivo and in vitro evidence for slipped mispairing in mammalian mitochondria. Proc Natl Acad Sci U S A 90:7671-5
Ghivizzani, S C; Mackay, S L; Madsen, C S et al. (1993) Transcribed heteroplasmic repeated sequences in the porcine mitochondrial DNA D-loop region. J Mol Evol 37:36-7
Hehman, G L; Hauswirth, W W (1992) DNA helicase from mammalian mitochondria. Proc Natl Acad Sci U S A 89:8562-6
Muise, R C; Hauswirth, W W (1992) Transcription in maize mitochondria: effects of tissue and mitochondrial genotype. Curr Genet 22:235-42
Chan, L; Zuker, M; Jacobson, A B (1991) A computer method for finding common base paired helices in aligned sequences: application to the analysis of random sequences. Nucleic Acids Res 19:353-8
Ashley, M V; Laipis, P J; Hauswirth, W W (1989) Rapid segregation of heteroplasmic bovine mitochondria. Nucleic Acids Res 17:7325-31
Laipis, P J; Van de Walle, M J; Hauswirth, W W (1988) Unequal partitioning of bovine mitochondrial genotypes among siblings. Proc Natl Acad Sci U S A 85:8107-10

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