Doctoral Dissertations

Date of Award

12-2020

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Major

Biochemistry and Cellular and Molecular Biology

Major Professor

Rachel Patton McCord

Committee Members

Adayabalam Balajee, Mariano Labrador, Bruce McKee, Albrecht von Arnim

Abstract

The human nucleus contains 2 meters of DNA which is intricately folded into a three-dimensional (3D) structure. It has become increasingly clear that this 3D structure plays an important role in the expression of genes. Proper gene expression is necessary for cellular homeostasis, cell state, and response to environmental/physical perturbations. Faithful repair of damage DNA damage is necessary to prevent genomic aberrations, such as translocations, which may lead to misregulation of gene expression. Hi-C, a sequencing technique that labels proximal chromatin interactions, provides a clearer picture of how the genome is spatially organized within the nucleus. Here, we discuss the effects that DNA damage has on 3D genome structure. Chapters 1 and 2 discuss the effects of ionizing radiation by X-rays and how it influences 3D genome architecture in wild-type and DNA repair deficient cells. Chapter 3 analyzes the 3D genome structure of Hutchinson-Gilford Progeria Syndrome patient cells and how it influences gene expression. Finally, Chapter 4 discusses the effects of osmotic stress on 3D genome organization. These findings suggest that different stressors which activate DNA damage pathways result in changes in 3D genome organization specific to the stress induced.

Orcid ID

https://orcid.org/0000-0002-4065-8742

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