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Functional analysis of the telomeras...
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Hsu, Min.
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Functional analysis of the telomerase regulatory factor Est 1 in Kluyveromyces lactis.
紀錄類型:
書目-電子資源 : Monograph/item
正題名/作者:
Functional analysis of the telomerase regulatory factor Est 1 in Kluyveromyces lactis./
作者:
Hsu, Min.
面頁冊數:
146 p.
附註:
Source: Dissertation Abstracts International, Volume: 76-01(E), Section: B.
Contained By:
Dissertation Abstracts International76-01B(E).
標題:
Biology, Molecular. -
電子資源:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3581772
ISBN:
9781321325751
Functional analysis of the telomerase regulatory factor Est 1 in Kluyveromyces lactis.
Hsu, Min.
Functional analysis of the telomerase regulatory factor Est 1 in Kluyveromyces lactis.
- 146 p.
Source: Dissertation Abstracts International, Volume: 76-01(E), Section: B.
Thesis (Ph.D.)--Weill Medical College of Cornell University, 2015.
This item is not available from ProQuest Dissertations & Theses.
Telorneres are special nucleoprotein structures located at the ends of chromosomes. Studies throughout the past decades have revealed many telomere protein components in different organisms. These telomere-bound proteins protect the ends of DNA against fusion, degradation, and recombination. In addition, a special reverse transcriptase, named telomerase, and its regulatory proteins have been also identified as factors responsible for telomere length maintenance. Because maintaining chromosome stability and integrity are important for normal cell functions, it is critical to understand the detailed mechanisms of these telomere-related factors.
ISBN: 9781321325751Subjects--Topical Terms:
1017719
Biology, Molecular.
Functional analysis of the telomerase regulatory factor Est 1 in Kluyveromyces lactis.
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Source: Dissertation Abstracts International, Volume: 76-01(E), Section: B.
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Adviser: Neal Lue.
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Thesis (Ph.D.)--Weill Medical College of Cornell University, 2015.
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Telorneres are special nucleoprotein structures located at the ends of chromosomes. Studies throughout the past decades have revealed many telomere protein components in different organisms. These telomere-bound proteins protect the ends of DNA against fusion, degradation, and recombination. In addition, a special reverse transcriptase, named telomerase, and its regulatory proteins have been also identified as factors responsible for telomere length maintenance. Because maintaining chromosome stability and integrity are important for normal cell functions, it is critical to understand the detailed mechanisms of these telomere-related factors.
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The major goal of this thesis is to understand the molecular basis and functional importance of one of the telomerase regulatory factors, Estl. The studies were conducted using a "non-standard" budding yeast, Kluyveromnyces lactis. Through biochemical and genetic analyses, we demonstrated and characterized the direct physical interaction between Estl and its binding partners, telomerase RNA and Cdcl3. We identified functional residues and regions of Estl required for the protein-RNA and protein-protein interactions. Our data indicate that both physical interactions are crucial for telomere maintenance. They also provide support for the recruitment model, which proposes that the interaction of Cdcl3 to Est1 plays a critical role in recruiting telomerase complex to the ends of telomeres. Moreover, we observed for the first time the formation of type I-like survivors in K. lactis estl Delta null post-senescent cultures, which provides support for a possible role of Estl in regulating telomeric DNA recombination.
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In addition, we showed that besides telornere maintenance, K. lactis Est1 participates in the nonsense-mediated mRNA decay (NMD) pathway. In Saccharomyces cerevisiae, this function is performed by Ebsl, an Est1 paralog. We therefore propose an evolutionary model in which the ancestral Est1 possesses both telomere maintenance and NMD functions. In this model, duplication and functional specialization of the ancestral EST1 in S. cerevisiae result in two paralogs, each serving only one of the original functions.
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Taken together, the thesis broadens our understanding of the molecular mechanisms of a telomerase regulatory factor and provides significant insights on how this factor contributes to telomere maintenance in cooperation with other important players in this pathway.
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