Thesis (M.S.)--University of Wisconsin--Madison, 1982. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 28-37).

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published_or_final_version / abstract / Pathology / Doctoral / Doctor of Philosophy

published_or_final_version / Pathology / Master / Master of Philosophy

The lexA41 (formerly tsl-l) mutant was previously isolated as a UV-resistant, temperature-sensitive derivative of its UV-sensitive lexA3(Ind⁻) parent. Cells exhibit a so-called "split-phenotype", a phenomenon in which only a subset of the SOS responses can be detected physiologically following inducing treatments. In this work, lexA41 has been cloned and sequenced; the mutant gene retains the lexA3 mutation (Gly to Asp at position 85) and has a second mutation, lexA41 (Ala to Thr at position 132). LexA41 protein is not cleaved by the RecA protein-catalyzed pathway in vivo, but the mutant protein is degraded by the Lon protease at both 32° and 42°C. β-galactosidase activities of lac fusions to thirteen different SOS promoters were measured at 30° and 42° to determine levels of expression and were found to vary considerably. LexA41 protein is deficient in repressor function. The temperature sensitive phenotype is due to increased expression of sulA, which encodes a division inhibitor, at 42°. Excision repair genes, including uvrA, uvrB and uvrD, are constitutively expressed at 30° accounting for the UV resistance of the lexA41 mutant, but the SOS mutagenesis operon, umuDC, is not adequately derepressed explaining the failure to induce mutagenesis in this background. This differential expression of SOS genes gives a plausible explanation of the "split-phenotype" associated with lexA41. In another set of experiments, I have examined the level of expression of the SOS regulon in cells lacking DNA adenine methylase activity (dam⁻). Mud (Ap, lac) fusions to several SOS operons (recA, lexA, uvrA, uvrB, uvrD, sulA, dinD, and dinF) were found to express higher levels of (beta)-galactosidase in dam⁻ strains than in isogenic dam⁺ strains. The attempted construction of dam⁻ strains that were also mutant in one of several SOS genes indicated that viability of methylase-deficient strains correlates with the inactivation of the SOS repressor (LexA protein). Consistent with this, the wild-type functions of two LexA-repressed genes (recA and ruv) appear to be required for viability of dam⁻ strains.

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The long-range structure of the Y chromosome alphoid satellite DNA has been determined in the cell lines 3E7 and OXEN. Variation in alphoid DNA block size and restriction enzyme sites were observed. The alphoid block size and restriction enzyme site variations were determined for a collection of 42 normal Y chromosomes. The alphoid DNA polymorphisms observed denned 24 Y chromosome alleles. Unexpectedly, the Y alphoid DNA alleles analysed revealed two distinct groups of Y chromosomes indicating that most of the Caucasian and Asian men analysed were descended from one of two males. The structure of the alphoid DNA was determined for 25 cell lines expected to contain abnormal Y chromosomes. Six of the cell lines lacked Y chromosomes. Four lacked both alphoid DNA and Y a centromere. 13 out of the remaining 15 Y chromosomes had centromeres and Y alphoid DNA block sizes and restriction enzyme site variation similar to that of normal Y chromosome alphoid DNA. Two of the abnormal cell lines had alphoid DNA blocks significantly different from the normal Y alphoid DNA structure. These results confirm that alphoid DNA is located very close to, or at the centromere and make it a prime candidate for a functional mammalian centromere sequence.

This thesis explores the variety of ways in which scientific views of genetic testing are portrayed in the realm of popular culture. As a case study, I have used the identification of the gene for hereditary stomach cancer which occurred in New Zealand in 1998, and was the result of a partnership between the affected whanau and scientists from the University of Otago. Both the empirical and theoretical findings of this project have shown how such accounts are not neutral or transparent. Rather, they are positioned to represent certain values and ideas, and this is even more evident when those affected are Maori. However, considering textual representations of the gene and cancer has revealed the importance of taking into account the fact that these 'things' are also physical and material. I consider the implications of this and consider the ways in which the whanau health workers negotiate the fetishism apparent in biomedicine. Despite its misgivings, biomedicine has immense benefits, some of which the whanau have manipulated and appropriated for their own good, although they do so on their own terms. Despite the many complexities involved in this case study, this is a positive and hopeful story where those involved in the stomach cancer gene project have emerged with improved solutions.

Thesis (Ph. D.)--University of Hong Kong, 2007. / Also available online.