C. elegans as a platform to characterize genes and therapeutics affecting genome stability
department or school: Science, Faculty of
data provider: DSpace
degree campus: UBCV
creator: Ye, Bin
issued: 2021-01-31T08:00:00Z
issued: 2019
related degree: Doctor of Philosophy - PhD
degree grantor: University of British Columbia
description: Genome stability is essential for survival in all living organisms. Perturbations of genome stability can lead to cancer and other diseases in human. Dysfunction of genome care-taking genes and exposure to external genotoxins are the two major drivers of genomic instability. Here, we used a model organism, C. elegans to study these factors and how they interact to affect genome stability. We first generated a chemi-genetic interaction map as a preliminary reference for characterizing genes and agents. From there, we elucidated the mechanisms of action for an emerging anticancer therapeutic CX-5461. CX-5461 turned out to be a multi-modal agent that exhibits genotypic sensitivity, mutagenicity and photosensitivity. Next, we identified a few genetic interactions within and between double-strand break repair pathways in C. elegans, which have implications in the response to both endogenous and exogenous DNA damage. We also characterized a less-understood gene SMRC-1, an annealing helicase. Loss of SMRC-1 results in copy number variations, and SMRC-1 is synthetic lethal with a number of DNA damage response genes. Our work concludes that C. elegans is a great platform to untangle the sophisticated complexity in genome maintenance, and provide meaningful insights for prospective anticancer therapeutic development.
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/72990
note: C. ELEGANS AS A PLATFORM TO CHARACTERIZE GENES AND THERAPEUTICS AFFECTING GENOME STABILITY by Bin Ye B.Sc., Xiamen University, 2014 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (Genome Science and Technology) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) December 2019 © Bin Ye, 2019 ii The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, the dissertation entitled: C. elegans as a platform to characterize genes and therapeutics affecting genome stability submitted by Bin Ye in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Genome Science and Technology Examining Committee: Philip Hieter, Medical Genetics Supervisor Stefan Taubert, Medical Genetics Supervisory Committee Member Michel Roberge, Biochemistry & Molecular Biology Supervisory Committee Member Peter Lansdorp, Medical Genetics University Examiner Don Moerman, Zoology University Examiner Additional Supervisory Committee Members: Samuel Aparicio, Pathology Supervisory Committee Member Supervisory Committee Member iii ABSTRACT Genome stability is essential for survival in all living organisms. Perturbations of genome stability can lead to cancer and other diseases in human. Dysfunction of genome care-taking genes and exposure to external genotoxins are the two major drivers of genomic instability. Here, we used a model organism, C. elegans to study these factors and how they interact to affect genome stability. We first generated a chemi-genetic interaction map as a preliminary reference for characterizing genes and agents. From there, we elucidated the mechanisms of action for an emerging anticancer therapeutic CX-5461. CX-5461 turned out to be a multi-modal agent that exhibits genotypic sensitivity, mutagenicity and photosensitivity. Next, we identified a few genetic interactions within…
has type: Thesis/Dissertation
date issued: 2020-05
is shown at: 10.14288/1.0387319
language: eng
degree discipline: Genome Science and Technology
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivatives 4.0 International
rights URI: http://creativecommons.org/licenses/by-nc-nd/4.0/
scholar level: Graduate
type: Text
identifier URI: http://hdl.handle.net/2429/72990