Identification and Characterization of Factors Involved in Sodium Selenite Toxicity
type: CreativeWork
description: Selenium (Se) is an essential micronutrient in many organisms. Despite being essential for some organisms, the range between its requirement and its toxicity is very narrow. Health benefits related to Se include the prevention of cancer, heart disease and neurodegenerative disorders. The inorganic form of Se, selenite (SeL) leads to reactive oxygen species (ROS) formation. Under physiological conditions, ROS modulate gene expression, active signaling cascades or even apoptosis. However, excessive ROS levels leads to oxidative stress, DNA damage and genome instability. Thus, ROS may be a tool to potentiate cancer therapy and in fact, SeL has been shown to exert a cytotoxic effect against different human cancers. In this thesis I have employed the yeast Saccharomyces cerevisiae as a model system to further investigate the molecular mechanisms involved in SeL detoxification and tolerance. In collaboration with the B. Morgan laboratory we find that SeL drives peroxide formation. Thus, based on available data on genes involved in resistance to selenide, selenite and peroxide, I identified new factors involved in SeL resistance. As a genetic read out I compared cell growth in SeL containing medium while as a molecular read out, I took advantage of a chromosome fragmentation assay to detect SeL-mediated DNA damage. A new factor involved in SeL resistance is the high mobility group (HMG) protein Hmo1. As Hmo1 has been shown to interact with Topoisomerase 2 (Top2) to organize chromatin organization, I further elaborated the role of Top2 in SeL mediated DNA damage formation. Notably, my results suggest that SeL-dependent chromosome fragmentation is enhanced in cells lacking Top2 activity. I further characterized factors involved in DNA damage response at the G1/S and S/G2 phase of the cell cycle needed to tolerate SeL. My data suggest that SeL leads to nicked DNA that is converted into double strands breaks (DSBs) when replicated. DNA cleavage appears to rely on factors that …
abstract: Selenium (Se) is an essential micronutrient in many organisms. Despite being essential for some organisms, the range between its requirement and its toxicity is very narrow. Health benefits related to Se include the prevention of cancer, heart disease and neurodegenerative disorders. The inorganic form of Se, selenite (SeL) leads to reactive oxygen species (ROS) formation. Under physiological conditions, ROS modulate gene expression, active signaling cascades or even apoptosis. However, excessive ROS levels leads to oxidative stress, DNA damage and genome instability. Thus, ROS may be a tool to potentiate cancer therapy and in fact, SeL has been shown to exert a cytotoxic effect against different human cancers. In this thesis I have employed the yeast Saccharomyces cerevisiae as a model system to further investigate the molecular mechanisms involved in SeL detoxification and tolerance. In collaboration with the B. Morgan laboratory we find that SeL drives peroxide formation. Thus, based on available data on genes involved in resistance to selenide, selenite and peroxide, I identified new factors involved in SeL resistance. As a genetic read out I compared cell growth in SeL containing medium while as a molecular read out, I took advantage of a chromosome fragmentation assay to detect SeL-mediated DNA damage. A new factor involved in SeL resistance is the high mobility group (HMG) protein Hmo1. As Hmo1 has been shown to interact with Topoisomerase 2 (Top2) to organize chromatin organization, I further elaborated the role of Top2 in SeL mediated DNA damage formation. Notably, my results suggest that SeL-dependent chromosome fragmentation is enhanced in cells lacking Top2 activity. I further characterized factors involved in DNA damage response at the G1/S and S/G2 phase of the cell cycle needed to tolerate SeL. My data suggest that SeL leads to nicked DNA that is converted into double strands breaks (DSBs) when replicated. DNA cleavage appears to rely on factors that …
author: Heluani Gahete, Hayat
language: eng
license: http://creativecommons.org/licenses/by-nc-nd/4.0/
date published: 2021-07-06
date modified: 2026-07-24T04:29:38Z
provider: Universidad de Sevilla
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Universidad de Sevilla

PropertyValue
property ID: Handle
value: https://hdl.handle.net/11441/127842