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Author ORCID Identifier

https://orcid.org/0000-0003-3542-0227

Document Type

Campus-Only Access for Five (5) Years

Degree Name

Doctor of Philosophy (PhD)

Degree Program

Molecular and Cellular Biology

Year Degree Awarded

2020

Month Degree Awarded

May

First Advisor

Peter Chien

Second Advisor

Sloan Siegrist

Third Advisor

Eric Strieter

Fourth Advisor

Erin Goley

Subject Categories

Microbial Physiology | Molecular Genetics | Systems Biology

Abstract

Protein degradation is an essential process in all organisms. The Lon protease, which is universally found in all domains of life, was the first energy dependent protease discovered. Yet, despite its earliest discovery its broadly conserved features have largely remained enigmatic. It is clear however, that Lon regulates key biological functions such as protein quality control and the DNA damage response. This thesis will discuss new insights into how Lon integrates its roles in protein quality control with those of the DNA damage response. In the first work, I will discuss how the conserved DNA binding properties of Lon are critical for turnover of persistent protein complexes that arise during DNA damage and in the second work, I will discuss how competition between misfolded proteins and natively folded substrates allows for sustained replication capacity during chronic protein quality control stress by adjusting nucleotide pools. The remaining chapters will focus on interesting observations that were discovered during these primary projects.

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Available for download on Saturday, May 08, 2021

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