Dissertations, Theses, and Capstone Projects
Date of Degree
2-2014
Document Type
Dissertation
Degree Name
Ph.D.
Program
Biology
Advisor
Diego Loayza
Subject Categories
Biology | Cell Biology | Molecular Biology
Keywords
POLA2, Polymerase alpha, Shelterin, Telomeres
Abstract
Telomeres consist of TTAGGG repeats, which end with a 3' G-overhang and are bound by a six-protein complex, known as Shelterin. In humans, telomeres shorten at each cell division, unless telomerase is expressed and able to add telomeric repeats to the 3' G-overhang. However, for effective telomere maintenance, the DNA strand complementary to that made by telomerase must be synthesized. In this study, I focused on the Polα/primase complex, in particular the subunits p68 (POLA2, the regulatory subunit) and p180 (Polα, the catalytic subunit), and their potential roles at telomeres. I was able to detect p180, p68 and OBFC1, a subunit in the CST complex, at telomeres in S phase using chromatin immunoprecipitations. I could also show that OBFC1, Shelterin and Polα/primase interact, revealing contacts occurring at telomeres. Finally, depletion of p68 by shRNA and p68 and p180 by siRNA, led to increased overhang amounts at telomeres. I propose a model in which Polα-primase is important for proper telomeric overhang processing, perhaps through fill-in synthesis. These results shed light on important events necessary for efficient telomere maintenance and protection.
Recommended Citation
Diotti, Raffaella, "Polymerase alpha components associate with telomeres to mediate overhang processing" (2014). CUNY Academic Works.
https://academicworks.cuny.edu/gc_etds/34
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