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The characterization of atm-1 in Caenorhabditis elegans Huang, Chin
Abstract
Loss of function of ATM (ataxia-telangiectasia, mutated) was discovered to be the genetic cause of the human disorder Ataxia-Telangiectasia (A-T). A-T is a rare, autosomal recessive human disorder that presents with multiple symptoms, including ataxia, telangiectasia, neurodegeneration, immunodeficiency, radiosensitivity, genomic instability, and a predisposition to developing cancer. The predicted ATM orthologue in Caenorhabditis elegans (C. elegans) is the gene atm-1. C. elegans is a model system that is easily amendable to molecular and genetic research. In this thesis, I have characterized the structure of atm-1 and examined its mutant phenotype. The predicted gene model for atm-1 was smaller than known orthologues. Using cDNA analysis and sequencing, I have shown that the three gene predictions atm-1, K10E9.1, and F56C11.4 make up the complete coding region. I observed differences from the original prediction including unpredicted splice sites and exonic sequences. A single atm-1 mutant allele, gk186, exists. I have shown that the gk186 deletion produces two alternative transcripts, one of which retains the protein kinase domain. Thus, in contrast to previous expectations that this mutation generated a loss of function phenotype, it is likely that it produces a protein with kinase function. The phenotype of the mutant is radiation sensitivity, as expected, but is not as sensitive as brd-1, another loss of function mutant in the same double strand break repair pathway. This result is consistent with partial function retention of atm-1. In addition, mutant atm-1 showed chromosomal instability in X-chromosome loss and subsequent sterility. Some of the mutational events were captured as lethals using the eT1 balancer system documenting a mutator phenotype of atm-1. Characterization of atm-1 gene function in C. elegans may provide additional information about its function in other organisms including humans.
Item Metadata
Title |
The characterization of atm-1 in Caenorhabditis elegans
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Creator | |
Publisher |
University of British Columbia
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Date Issued |
2011
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Description |
Loss of function of ATM (ataxia-telangiectasia, mutated) was discovered to be the genetic cause of the human disorder Ataxia-Telangiectasia (A-T). A-T is a rare, autosomal recessive human disorder that presents with multiple symptoms, including ataxia, telangiectasia, neurodegeneration, immunodeficiency, radiosensitivity, genomic instability, and a predisposition to developing cancer. The predicted ATM orthologue in Caenorhabditis elegans (C. elegans) is the gene atm-1. C. elegans is a model system that is easily amendable to molecular and genetic research. In this thesis, I have characterized the structure of atm-1 and examined its mutant phenotype. The predicted gene model for atm-1 was smaller than known orthologues. Using cDNA analysis and sequencing, I have shown that the three gene predictions atm-1, K10E9.1, and F56C11.4 make up the complete coding region. I observed differences from the original prediction including unpredicted splice sites and exonic sequences. A single atm-1 mutant allele, gk186, exists. I have shown that the gk186 deletion produces two alternative transcripts, one of which retains the protein kinase domain. Thus, in contrast to previous expectations that this mutation generated a loss of function phenotype, it is likely that it produces a protein with kinase function. The phenotype of the mutant is radiation sensitivity, as expected, but is not as sensitive as brd-1, another loss of function mutant in the same double strand break repair pathway. This result is consistent with partial function retention of atm-1. In addition, mutant atm-1 showed chromosomal instability in X-chromosome loss and subsequent sterility. Some of the mutational events were captured as lethals using the eT1 balancer system documenting a mutator phenotype of atm-1. Characterization of atm-1 gene function in C. elegans may provide additional information about its function in other organisms including humans.
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Genre | |
Type | |
Language |
eng
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Date Available |
2011-06-08
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Provider |
Vancouver : University of British Columbia Library
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Rights |
Attribution-NonCommercial-NoDerivatives 4.0 International
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DOI |
10.14288/1.0071869
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URI | |
Degree | |
Program | |
Affiliation | |
Degree Grantor |
University of British Columbia
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Graduation Date |
2011-11
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Campus | |
Scholarly Level |
Graduate
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Rights
Attribution-NonCommercial-NoDerivatives 4.0 International