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Coenzyme Q (ubiquinone or UQ) is a prenylated benzoquinone lipid that is found in membranes throughout the cell, and functions in a wide variety of enzyme-mediated redox reactions. One of the primary roles of UQ is its involvement in respiratory metabolism, where it functions in the inner mitochondrial membrane of eukaryotic cells as a transporter of electrons and protons in complexes II and III. The biosynthesis of UQ involves two separate O-methylation steps. Coq3p which is 40% identical to the Escherichia coli O-methyltransferase, UbiG, catalyzes both O-methylation steps. / In order to elucidate the function of genes involved in UQ biosynthesis, a coq-3 null mutant in the nematode C. elegans has been isolated by mean of reverse genetics. About 3,000,000 haploid genomes have been screened and a deletion in this gene isolated. Many technical difficulties have been encountered and modification concerning the details of the screening protocol was required to bypass them. The loss of coq-3 function in nematodes leads to developmental arrest and sterility, even when the worms are fed with bacteria that produce UQ. This demonstrates that UQ is required for the development and fertility of the worms.

Programmed cell death (PCD or apoptosis) is an evolutionarily conserved, genetically controlled suicide mechanism for cells, which when deregulated, can lead to developmental defects, cancers and degenerative diseases. In C. elegans, DNA damage induces germ cell death by signaling through cep-1/p53 ultimately leading to the activation of the CED-3/caspase. It has been hypothesized that the major regulatory events controlling cell death occur by cell autonomous mechanisms, that is within the dying cell. In support of this, genetic studies in C. elegans have shown that the core apoptosis pathway genes ced-4/APAF1 and ced-3/caspase are required in cells fated to die. However, it is not known whether the upstream signals that activate apoptosis function in a cell autonomous manner. Here I show that two genes, kri-1, an ortholog of KRIT1/CCM1 that is mutated in the human neurovascular disease cerebral cavernous malformations (CCMs) and daf-2, an insulin-like receptor, are required to activate DNA damage-dependent cell death independently of cep-1/p53. Interestingly, I found that both genes can regulate cell death in a non-autonomous manner, revealing a novel role for non-dying cells in eliciting death in response to DNA damage.

Programmed cell death (PCD or apoptosis) is an evolutionarily conserved, genetically controlled suicide mechanism for cells, which when deregulated, can lead to developmental defects, cancers and degenerative diseases. In C. elegans, DNA damage induces germ cell death by signaling through cep-1/p53 ultimately leading to the activation of the CED-3/caspase. It has been hypothesized that the major regulatory events controlling cell death occur by cell autonomous mechanisms, that is within the dying cell. In support of this, genetic studies in C. elegans have shown that the core apoptosis pathway genes ced-4/APAF1 and ced-3/caspase are required in cells fated to die. However, it is not known whether the upstream signals that activate apoptosis function in a cell autonomous manner. Here I show that two genes, kri-1, an ortholog of KRIT1/CCM1 that is mutated in the human neurovascular disease cerebral cavernous malformations (CCMs) and daf-2, an insulin-like receptor, are required to activate DNA damage-dependent cell death independently of cep-1/p53. Interestingly, I found that both genes can regulate cell death in a non-autonomous manner, revealing a novel role for non-dying cells in eliciting death in response to DNA damage.

Thesis (Ph. D.)--University of Wyoming, 2006. / Title from PDF title page (viewed on June 16, 2008). Includes bibliographical references (p. 60-72).

Thesis (Ph. D.)--University of Virginia, 1998. / Includes bibliographical references (208-224). Also available online through Digital Dissertations.

Thesis (M.Phil.)--Hong Kong University of Science and Technology, 2009. / Includes bibliographical references (p. 127-137).

Thesis (Ph.D.). / Written for the Dept. of Biology. Title from title page of PDF (viewed 2009/06/09). Includes bibliographical references.

Thesis (Ph. D.)--Rutgers University, 2009. / "Graduate Program in Neuroscience." Includes bibliographical references.

Thesis (M. Phil.)--Hong Kong University of Science and Technology, 2002. / Includes bibliographical references (leaves 116-121). Also available in electronic version. Access restricted to campus users.