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Genetic analysis of TRA1 function in...

Van Buskirk, Heather Anne.

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Genetic analysis of TRA1 function in Saccharomyces cerevisiae.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	Genetic analysis of TRA1 function in Saccharomyces cerevisiae./
作者:	Van Buskirk, Heather Anne.
面頁冊數:	286 p.
附註:	Adviser: Michael Cole.
Contained By:	Dissertation Abstracts International62-11B.
標題:	Biology, Genetics. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3033045
ISBN:	0493457925

Genetic analysis of TRA1 function in Saccharomyces cerevisiae.
Van Buskirk, Heather Anne.

Genetic analysis of TRA1 function in Saccharomyces cerevisiae. - 286 p.

Adviser: Michael Cole.

Thesis (Ph.D.)--Princeton University, 2002.

We have isolated a novel 434 kDa protein, TRRAP, that interacts specifically with the amino terminus of the c-Myc oncoprotein and whose function is required for the c-Myc oncogenic pathway. The yeast homologue of TRAAP, <italic>TRA1 </italic>, has recently been identified as a component of two large histone acetyltransferase complexes, SAGA and NuA4. In this study, I have generated five temperature sensitive mutant alleles of <italic>TRA1</italic> and have shown that yeast strains bearing these mutant alleles arrest in the G2/M phase of the cell cycle following a shift to the non-permissive temperature. Furthermore, these mutants show increased sensitivity to agents that induce DNA damage or replication blocks, including methylmethane sulphonic acid, hydroxyurea, and ultraviolet irradiation, suggesting a role for <italic>TRA1</italic> in the cellular response to DNA damage or incompletely replicated DNA. In addition, <italic> tra1</italic> mutants show defects in transcriptional silencing at both the telomeres and within the rDNA arrays. The fact that a second component of the NuA4 complex, <italic>ESA1</italic>, also shares this phenotype suggests that both <italic>TRA1</italic> and <italic>ESA1</italic> exert their effects on silencing via the NuA4 complex, perhaps by the acetylation of histones. Northern blot analyses demonstrated that the expression of several mRNAs is defective in <italic>tra1</italic> mutants upon shifting to the non-permissive temperature. Furthermore, genome-wide expression analysis using Affymetrix GeneChip technology (Affymetrix, Inc., Santa Clara, CA) showed that the <italic> tra1-3<super>ts</super></italic> mutant is defective in the expression of approximately 4% of the open reading frames in the yeast genome. Finally, the genome-wide expression analysis performed here revealed that the extent of overlap between genes whose mRNA expression is <italic>TRA1</italic>-dependent, <italic> ESA1</italic>-dependent, and <italic>GCN5</italic>-dependent is relatively small, arguing for novel functions of <italic>TRA1</italic> that are independent of both <italic>GCN5</italic> and <italic>ESA1</italic>.

ISBN: 0493457925Subjects--Topical Terms:

1017730
Biology, Genetics.

Genetic analysis of TRA1 function in Saccharomyces cerevisiae.
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520 $a We have isolated a novel 434 kDa protein, TRRAP, that interacts specifically with the amino terminus of the c-Myc oncoprotein and whose function is required for the c-Myc oncogenic pathway. The yeast homologue of TRAAP, <italic>TRA1 </italic>, has recently been identified as a component of two large histone acetyltransferase complexes, SAGA and NuA4. In this study, I have generated five temperature sensitive mutant alleles of <italic>TRA1</italic> and have shown that yeast strains bearing these mutant alleles arrest in the G2/M phase of the cell cycle following a shift to the non-permissive temperature. Furthermore, these mutants show increased sensitivity to agents that induce DNA damage or replication blocks, including methylmethane sulphonic acid, hydroxyurea, and ultraviolet irradiation, suggesting a role for <italic>TRA1</italic> in the cellular response to DNA damage or incompletely replicated DNA. In addition, <italic> tra1</italic> mutants show defects in transcriptional silencing at both the telomeres and within the rDNA arrays. The fact that a second component of the NuA4 complex, <italic>ESA1</italic>, also shares this phenotype suggests that both <italic>TRA1</italic> and <italic>ESA1</italic> exert their effects on silencing via the NuA4 complex, perhaps by the acetylation of histones. Northern blot analyses demonstrated that the expression of several mRNAs is defective in <italic>tra1</italic> mutants upon shifting to the non-permissive temperature. Furthermore, genome-wide expression analysis using Affymetrix GeneChip technology (Affymetrix, Inc., Santa Clara, CA) showed that the <italic> tra1-3<super>ts</super></italic> mutant is defective in the expression of approximately 4% of the open reading frames in the yeast genome. Finally, the genome-wide expression analysis performed here revealed that the extent of overlap between genes whose mRNA expression is <italic>TRA1</italic>-dependent, <italic> ESA1</italic>-dependent, and <italic>GCN5</italic>-dependent is relatively small, arguing for novel functions of <italic>TRA1</italic> that are independent of both <italic>GCN5</italic> and <italic>ESA1</italic>.
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