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The Chromatin Association Profile of Trypanosoma brucei RAP1 and Trypanosoma brucei TIF2's Role in Telomere DNA Replication

Wong, Janine C
http://rave.ohiolink.edu/etdc/view?acc_num=csu1533215961103856

Abstract Details

2018, Master of Science in Biology, Cleveland State University, College of Sciences and Health Professions.
Trypanosoma brucei is a protozoan parasite that causes fatal human African trypanosomiasis and regularly switches its major surface antigen, VSG, to evade the host immune response. VSGs are exclusively expressed monoallelically from subtelomeric VSG expression sites (ESs). Telomeres are vital DNA/protein complexes that protect the ends of chromosomes from DNA damage. T. brucei telomeric proteins include TTAGGG-repeat binding factor (TRF), repressor activator protein-1 (RAP1), and TRF-interacting factor 2 (TIF2). These telomere proteins have several important functions in T. brucei and are important for the regulation of VSG expression and switching. My thesis will focus on the two telomere proteins TbRAP1 and TbTIF2. Project 1: The Chromatin Association Profile of Trypanosoma brucei RAP1 We identified TbRAP1 as a telomere protein, and have shown that depletion of TbRAP1 led to an increased VSG switching frequency as well as derepression of telomeric silent VSGs. In both yeast and in mammalian cells, RAP1 homologues have been shown to have extra-telomeric functions. In yeast, ScRAP1 regulates genes involved in glycolysis. In mammalian cells, RAP1 is an I kappa B kinase (IKK) adaptor and regulates NF¿B-dependent gene expression. To explore whether TbRAP1 has similar roles at non-telomere loci, we set out to investigate the chromatin association profile of TbRAP1 through chromatin immunoprecipitation and high throughput sequencing (ChIP-seq). Project 2: Trypanosoma brucei TIF2’s role in Telomere DNA Replication The maintenance of subtelomere integrity is important for T. brucei because VSG is expressed from the subtelomeric VSG expression sites. We found that depletion of the telomere protein TbTIF2 leads to an increase in double stranded breaks (DSBs) in the subtelomere and elevated VSG switching frequency. It is known that telomere proteins in human cells and yeasts are required for telomere DNA replication. Additionally, replication fork stalling often leads to DSBs. Therefore, we hypothesize that TbTIF2 plays an important role in proper telomeric DNA replication. To investigate TbTIF2’s role in telomere DNA replication, we are currently establishing a Single Molecule Analysis of Replicating DNA (SMARD) Assay and an EdU labeling assay in our lab to examine the effects of TbTIF2 depletion on telomere replication.
Bibo Li (Advisor)
Aaron Severson (Committee Member)
Girish Shukla (Committee Member)
Biology

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Citations

  • Wong, J. C. (2018). The Chromatin Association Profile of Trypanosoma brucei RAP1 and Trypanosoma brucei TIF2's Role in Telomere DNA Replication [Master's thesis, Cleveland State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=csu1533215961103856

    APA Style (7th edition)

  • Wong, Janine. The Chromatin Association Profile of Trypanosoma brucei RAP1 and Trypanosoma brucei TIF2's Role in Telomere DNA Replication. 2018. Cleveland State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=csu1533215961103856.

    MLA Style (8th edition)

  • Wong, Janine. "The Chromatin Association Profile of Trypanosoma brucei RAP1 and Trypanosoma brucei TIF2's Role in Telomere DNA Replication." Master's thesis, Cleveland State University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=csu1533215961103856

    Chicago Manual of Style (17th edition)

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This open access ETD is published by Cleveland State University and OhioLINK.