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Dna Replication Challenges: Telomeres And R Loops, Shankar Parajuli
Dna Replication Challenges: Telomeres And R Loops, Shankar Parajuli
Arts & Sciences Electronic Theses and Dissertations
Faithful DNA replication and repair are essential for maintaining genome stability and preventing various diseases including cancer. Both processes are executed by numerous redundant mechanisms to ensure that these processes are uninterrupted even when a primary mechanism fails. Despite this, they are not immune to challenges and failures leading to DNA damage and genome instability. These problems are more evident at the difficult-to-replicate regions of the genome such as the telomeres that cap and protect linear chromosome ends. Additionally, topological structures such as RNA:DNA hybrids, commonly referred to as R loops, can also present severe challenges to the DNA replication …
Mechanisms And Regulation Of Resection In Dna Damage Response, Sharad C. Paudyal
Mechanisms And Regulation Of Resection In Dna Damage Response, Sharad C. Paudyal
Arts & Sciences Electronic Theses and Dissertations
Deoxyribonucleic acid (DNA) encodes genetic information essential for cell survival and function. However, it is constantly under assault from endogenous and exogenous damaging agents that not only threaten our own survival but also affect the faithful transmission of genetic information to our offspring. Double-strand breaks (DSBs) are one of the most hazardous forms of DNA damage, which if unrepaired or improperly repaired could lead to plethora of systemic human diseases including cancer. To deal with this problem, cells have evolved with a mechanism called DNA damage response (DDR) to detect, signal, and repair the breaks by inducing multiple cellular events. …
Designing Epigenome Editing Tools To Understand The Functional Role Of Dna Methylation Changes In Cancer, James Mcdonald
Designing Epigenome Editing Tools To Understand The Functional Role Of Dna Methylation Changes In Cancer, James Mcdonald
Arts & Sciences Electronic Theses and Dissertations
DNA methylation is known to silence gene expression in the context of imprinting, X-chromosome inactivation, and retrotransposon silencing. However, the role of DNA methylation in silencing gene expression outside of these contexts is not fully understood. This is especially true in diseases such as cancer, where normal DNA methylation patterns are significantly altered. In breast cancer as well as nearly all cancer types, most of the genome loses DNA methylation while small regions of the genome gain methylation. DNA methylation generally correlates with decreased gene expression when present at a gene promoter. Therefore, these regions of hypo- and hyper-methylation may …
Mitochondrial Dynamics Controls T Cell Fate Through Metabolic Programming, Michael Buck
Mitochondrial Dynamics Controls T Cell Fate Through Metabolic Programming, Michael Buck
Arts & Sciences Electronic Theses and Dissertations
Activated effector T (TE) cells augment anabolic pathways of metabolism, such as aerobic glycolysis, while memory T (TM) cells engage catabolic pathways, like fatty acid oxidation (FAO). However, signals that drive these differences remain unclear. Mitochondria are metabolic organelles that actively transform their ultrastructure. Therefore, we questioned whether mitochondrial dynamics controls T cell metabolism. We show that TE cells have punctate mitochondria, while TM cells maintain fused networks. The fusion protein Opa1 is required for TM, but not TE cells after infection, and enforcing fusion in TE cells imposes TM cell characteristics and enhances antitumor function. Our data suggest that, …