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Contributions of DNA polymerase delt...
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Lawrence, Nicole A.
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Contributions of DNA polymerase delta proofreading to replication fidelity in Saccharomyces Cerevisiae.
紀錄類型:
書目-電子資源 : Monograph/item
正題名/作者:
Contributions of DNA polymerase delta proofreading to replication fidelity in Saccharomyces Cerevisiae./
作者:
Lawrence, Nicole A.
面頁冊數:
155 p.
附註:
Source: Dissertation Abstracts International, Volume: 64-02, Section: B, page: 0527.
Contained By:
Dissertation Abstracts International64-02B.
標題:
Biology, Genetics. -
電子資源:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3080608
Contributions of DNA polymerase delta proofreading to replication fidelity in Saccharomyces Cerevisiae.
Lawrence, Nicole A.
Contributions of DNA polymerase delta proofreading to replication fidelity in Saccharomyces Cerevisiae.
- 155 p.
Source: Dissertation Abstracts International, Volume: 64-02, Section: B, page: 0527.
Thesis (Ph.D.)--The University of Utah, 2003.
Each time a cell divides it must create an accurate copy of its genetic information. Faithful DNA replication is achieved by a series of overlapping mechanisms. The DNA polymerase selectively inserts nucleotides into the growing strand of DNA. Occasional misinsertions are extended slowly, creating the opportunity for removal by 3' to 5' exonucleolytic proofreading. Replication errors that escape proofreading are subject to mismatch repair. This research has focused on eukaryotic proofreading and employs the simple model eukaryote, S. cerevisiae. Mutational analysis of the exonuclease (Exo) domain of one of the main replicative polymerases in yeast, polymerase delta (Pol delta), highlights the importance of the conserved Exo carboxylates to proofreading function. Two Exo subdomains were identified as important to replication fidelity by screening alanine-scanning mutants for mutator phenotypes. This research describes the cooperative relationship between Pol delta proofreading and Msh6-mediated mismatch repair in repairing polymerase errors and utilizes this relationship to uncover weak Pol delta mutator alleles. An inverse correlation was noted between mutation rate and cell growth; the most mild msh6Delta Pol delta mutator cells grow normally; msh6Delta moderate Pol delta mutator cells grow slowly; and the strongest msh6Delta Pol delta mutator cells do not grow. One explanation of these data is that the cells are experiencing error catastrophe, a phenomena in which cells die by lethal mutagenesis. Examination of rare, growing msh6Delta strong Pol delta mutator colonies led to the discovery of second site mutations in Pol delta that restore growth to msh6Delta strong Pol delta mutator cells and reduce the mutation rate of MSH6 + strong Pol delta mutator cells. The rescue of growth in strong mutator strains by antimutator alleles lends further support to the notion that msh6Delta strong Pol delta mutator yeast strains are experiencing error catastrophe, and highlights the vital role of polymerase proofreading in DNA replication fidelity.Subjects--Topical Terms:
1017730
Biology, Genetics.
Contributions of DNA polymerase delta proofreading to replication fidelity in Saccharomyces Cerevisiae.
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Each time a cell divides it must create an accurate copy of its genetic information. Faithful DNA replication is achieved by a series of overlapping mechanisms. The DNA polymerase selectively inserts nucleotides into the growing strand of DNA. Occasional misinsertions are extended slowly, creating the opportunity for removal by 3' to 5' exonucleolytic proofreading. Replication errors that escape proofreading are subject to mismatch repair. This research has focused on eukaryotic proofreading and employs the simple model eukaryote, S. cerevisiae. Mutational analysis of the exonuclease (Exo) domain of one of the main replicative polymerases in yeast, polymerase delta (Pol delta), highlights the importance of the conserved Exo carboxylates to proofreading function. Two Exo subdomains were identified as important to replication fidelity by screening alanine-scanning mutants for mutator phenotypes. This research describes the cooperative relationship between Pol delta proofreading and Msh6-mediated mismatch repair in repairing polymerase errors and utilizes this relationship to uncover weak Pol delta mutator alleles. An inverse correlation was noted between mutation rate and cell growth; the most mild msh6Delta Pol delta mutator cells grow normally; msh6Delta moderate Pol delta mutator cells grow slowly; and the strongest msh6Delta Pol delta mutator cells do not grow. One explanation of these data is that the cells are experiencing error catastrophe, a phenomena in which cells die by lethal mutagenesis. Examination of rare, growing msh6Delta strong Pol delta mutator colonies led to the discovery of second site mutations in Pol delta that restore growth to msh6Delta strong Pol delta mutator cells and reduce the mutation rate of MSH6 + strong Pol delta mutator cells. The rescue of growth in strong mutator strains by antimutator alleles lends further support to the notion that msh6Delta strong Pol delta mutator yeast strains are experiencing error catastrophe, and highlights the vital role of polymerase proofreading in DNA replication fidelity.
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