No description available.

No description available.

No description available.

The effects of a newly mapped DNA repair-defective mutant, uvsI, on mutagen sensitivities and mutation were investigated. Results showed that uvsI differs for most of the investigated properties from other uvs mutants of A. nidulans which are known to belong to three different epistatic groups, "UvsF", "UvsC", and "UvsB". Most of these mutants are sterile and many of them alter mitotic recombination frequencies, while uvsI exhibits normal levels of meiotic and mitotic recombination. In addition, uvsI strains are not more sensitive than wild type to MMS (methyl methanesulfonate) to which all other uvs strains are sensitive. However, the uvsI mutant was found to be very sensitive to the killing effects of UV light and the chemical mutagen, 4-NQO (4-nitro-quinoline-N-oxide). In line with the distinct phenotype of uvsI, no epistatic interactions were found for this mutant with any members of the established three epistatic groups. The effects of uvsI on mutagenesis are highly specific and dependent on the mutational test systems. In the uvsI mutant, two types of forward mutation were not affected, but spontaneous and UV-induced reversion frequencies of choA1 and pabaA1 were significantly reduced. Specific effects were further demonstrated in reversion tests of various sC alleles originally isolated as selenate resistant mutants by treatment with EMS (ethyl methanesulfonate), which leads mainly to G:C to A:T transitions. After EMS treatment uvsI mutants showed highly reduced reversion frequencies for all these sC alleles (except one) compared to $uvs sp+$ strains. These results suggest that the uvsI mutation may be defective in AT to GC transition mutagenesis, while increasing transversion(s) from A:T base pairs. In contrast, uvsI affected the frequencies of spontaneous and UV-induced reversions for these sC alleles in a variety of ways. Thus, uvsI may well represent a fourth functional and epistatic group of DNA repair and possibly be involved in a minor mutagenic DN

No description available.

No description available.

No abstract available. / Thesis (Ph.D.)-University of Natal, Durban, 1983.

No description available.

No description available.

Metastasis is the spread of cancer cells from the primary tumor to distant sites. It is the most dangerous attribute of cancer, and also the principle cause of cancerrelated morbidity and mortality. Metastasis suppressor genes are a group of genes that suppress tumor metastasis without significant effect on tumorigenicity. NM23 was the first identified metastasis suppressor gene, and loss of its expression is a frequent hallmark of metastatic growth in multiple cancers (e.g. melanoma, carcinomas of breast, stomach and liver). NM23-H1 possesses at least three enzymatic activities, including nucleoside diphosphate kinase (NDPK), histidine kinase (hisK), and a more recently described 3f-5f exonuclease (EXO). While the hisK has been shown to be linked to the suppression of cell motility, the NDPK has been reported to be unrelated to the suppression of metastatic potential indirectly. Relevance of EXO has not been addressed. Other known 3f-5f exonuclease are closely associated with DNA repair functions, suggesting NM23-H1 may suppress mutations required for metastasis. As a transcription factor, NM23 has been shown to modestly downregulate the transcription on PDGF-A chain, a growth factor oncogene, either alone or in association with another transcriptional factor, Pur@. At the same time, identification of NM23-H1 as a 3f-5fexonuclease suggests the role of NM23-H1 in DNA repair. Etoposide and cisplatin elicited nuclear translocation of H1 within 4 h in HeLa and HepG2 cells, seen as accumulation of H1 in small intranuclear foci, strongly suggesting the DNA repair function of H1. To investigate the enzymatic function contributing to metastasis suppressor activity of H1, complementation system was used by transfecting NM23-H1 with individually disrupted enzymatic function into 2 melanoma cell lines, 1205LU and WM793. Overexpression of H1 in 1205LU suppressed lung metastasis in vivo without effect on indices of transformation (e.g. proliferation, soft agar colonization). EXO- deficient H1 and NDPK-deficient H1 lost suppression of lung metastasis, while hisK-deficient H1 maintained suppressor activity. Consistent with the results in 1205LU cells, EXO-deficient H1 and NDPKdeficient H1 lost suppression of the progression of WM793 cells in protein-free medium, while WT and hisK-deficient H1 prevented the progression. Taken together, these data suggest that the NDPK and/or 3f-5fEXO activity of H1 inhibits the progression of premetastatic cells to the metastatic phenotype, possibly via a DNA repair function or other structural transactions with DNA.