Journey of telomerase : telomerase trafficking and telomere length regulation in human cells

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Abstract/Contents

Abstract
Telomeres are specialized chromatin regions at the ends of linear chromosomes of all eukaryotic cells. The proper regulation of telomere structure and telomere length is critical for genome integrity, cellular survival and organismal health. In all vertebrates, the 'telomere maintenance' pathway is coordinated by the telomerase complex and the shelterin complex, respectively, along with a large number of accessory factors. Although the importance of this pathway in human health, such as aging and cancer development is being increasingly recognized, we currently lack a coherent and detailed understanding on the mechanisms of telomere maintenance at the molecular level, particularly on the interplay between various components of the telomerase and shelterin complex in coordinating the discrete steps of telomere regulation, such as extension, capping and processing. The work described in this dissertation aims to fill some of the knowledge gap in telomerase and telomere research. We first present findings on a novel telomerase component TCAB1 and its role in telomerase trafficking and the pathology of a form of inherited 'telomere disease', dyskeratosis congenita. Next, we report the identification of TPP1-OB fold as the bona fide telomerase recruiter within the shelterin complex. Finally we present evidence on a novel, yet-to-be characterized 'post-recruitment' step in telomerase regulation mediated by another shelterin component, TIN2 that is mutated in human telomere diseases.

Description

Type of resource text
Form electronic; electronic resource; remote
Extent 1 online resource.
Publication date 2014
Issuance monographic
Language English

Creators/Contributors

Associated with Lei Zhong, Franklin
Associated with Stanford University, Cancer Biology Program.
Primary advisor Artandi, Steven E
Thesis advisor Artandi, Steven E
Thesis advisor Bassik, Michael
Thesis advisor Sage, Julien
Thesis advisor Straight, Aaron, 1966-
Thesis advisor Teruel, Mary
Advisor Bassik, Michael
Advisor Sage, Julien
Advisor Straight, Aaron, 1966-
Advisor Teruel, Mary

Subjects

Genre Theses

Bibliographic information

Statement of responsibility Franklin Lei Zhong.
Note Submitted to the Program in Cancer Biology.
Thesis Thesis (Ph.D.)--Stanford University, 2014.
Location electronic resource

Access conditions

Copyright
© 2014 by Lei Zhong
License
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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