Item Details

title

TREX1: Functionality and Relevance to Disease

author

Zalesak, Owen

abstract

Three Prime Repair Exonuclease 1 (TREX1) is the major 3’ exonuclease within the cell. TREX1 is a dimeric protein, with each monomer comprising of two major domains, the N-terminal catalytic domain and the C-terminal targeting domain. The C-terminal targeting domain localizes TREX1 to the perinuclear space of the cytosol, with the domain anchored within the ER/Nuclear membrane. TREX1 activity degrades single stranded (ssDNA) and double stranded (dsDNA) in the cytosol, preventing signaling from the cyclic guanine and adenine monophosphate synthase-stimulator of interferon genes (cGAS-STING) pathway. Mutations in TREX1 lead to several diseases, such as Aicardi–Goutières syndrome (AGS) and Retinal Vasculopathy with Cerebral Leukodystrophy (RVCL), which are all characterized by an intense systematic auto-immune response. However, triggering an acute immune response could be beneficial in certain disease states such as cancer. Inhibiting TREX1 could allow better detection of cancer cells by activating cGAS-STING signaling. TREX1 also has a potential involvement in other inflammation driven conditions such as Diabetes Mellitus (DM). Patients with DM have increased reactive oxygen species (ROS) conditions within their cells leading to oxidative stress. This oxidative stress could be leading to multiple pathways that either inhibit or degrade TREX1 leading to cGAS-STING signaling.

subject

Crystallography

Exonuclease

Inflammation

Inhibitor

Oxidative Stress

TREX1

contributor

Hollis, Thomas (advisor)

Lowther, W. Todd (committee member)

date

2023-07-25T17:48:42Z (accessioned)

2023 (issued)

degree

Biochemistry and Molecular Biology (discipline)

embargo

2024-06-06 (terms)

2024-06-06 (liftdate)

identifier

http://hdl.handle.net/10339/102262 (uri)

language

en (iso)

publisher

Wake Forest University

type

Thesis