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Title: The role of the cell cycle in lethality and mutagenic change in yeast
Author: Hussain, A. H. M.
Awarding Body: University College of Swansea
Current Institution: Swansea University
Date of Award: 1981
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This study was mainly concerned with cell lethality and mutation induction in the haploid S. cerevisiae during cycle, which was obtained by the use of a zonal rotor centrifugation, to separate the exponential phase cells into discrete periods according to age. Cultures with different DNA repair ability have been examined after treatment with physical (UV) and chemical (NA, EMS, MMS) mutagens. All the cultures used (wild type, excision deficient mutants and double mutants, defective in error-prone and post replication repair), showed their highest sensitivity in the G1 phase but variable resistance during the S (DNA synthesis) and G2 (post DNA synthesis) phases. It became apparent that the excision repair is the only error-free repair pathway operating in the G1 phase, after results were obtained showing that maximum mutation induction in excision deficient mutants and minimum mutation induction in wild type strain (excision proficient) occurred after chemical. mutagenesis. The maximum mutation induction was probably due to error-prone repair operating when the excision repair was absent in radl and 3 mutants, while minimum mutation induction in the wild type may be attributed to the high excision repair efficiency. After UV irradiation the mutation induction was at a maximum in the radl, rad3 and wild type cultures, which was probably caused by the inability of excision repair (wild type) to deal with a large number of pyrimidine dimers. Therefore, error-prone repair takes place in these cultures. Post-replication repair seems to be the main error-free repair pathway in the S and G2 phases, as they show similar cell resistance and mutation induction in the wild type, radl and rad3 cultures. In the double mutant when the cell was defective in post-replication repair, the G2 phase showed high cell sensitivity as well as maximum mutation induction. G1 phase cells also displayed very different characteristics to the stationary phase cells. After X-ray treatment, the exponential phase of the excision deficient mutants shows higher sensitivity than the stationary phase, and both wild type growth phases. After UV irradiation, the exponential phase shows higher resistance than the stationary phase in all the cultures except the double mutant. After chemical mutagens treatment, the exponential phase shows higher sensitivity than the stationary phase in all the cultures. Triple mutants showed the greatest differences in sensitivity between the two phases especially after alkylating agents. The relative effectiveness of the individual mutagens with regard to mutation induction were as follows: UV > NA > MMS > EMS. The relationship between UV and NA depends upon the survival rate of different strains.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available