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Novel Insights Into The Multifaceted Roles Of Blm In The Maintenance Of Genome Stability, Vivek M. Shastri Apr 2019

Novel Insights Into The Multifaceted Roles Of Blm In The Maintenance Of Genome Stability, Vivek M. Shastri

USF Tampa Graduate Theses and Dissertations

Genomic instability is a hallmark of disorders in which DNA replication and repair genes are dysfunctional. The tumor suppressor RECQ helicase gene BLM encodes the 3’-5’ DNA Bloom syndrome helicase BLM, which plays important roles during DNA replication, recombination and repair to maintain genome stability. Mutations within BLM cause Bloom syndrome, an autosomal recessive disorder characterized by growth defects, immunodeficiency, >10-fold higher sister chromatid exchange compared to normal cells, and an increased predisposition to a wide range of cancers from an early age. Single nucleotide polymorphisms or SNPs in BLM have been reported to be associated with susceptibility to a …


Nascent Dna Proteomics Analysis Uncovers Dna Replication Dynamics In The Human Pathogen Trypanosoma Brucei, Maria Rocha Granados Mar 2019

Nascent Dna Proteomics Analysis Uncovers Dna Replication Dynamics In The Human Pathogen Trypanosoma Brucei, Maria Rocha Granados

Doctoral Dissertations

DNA is the substrate of many cellular processes including DNA replication, transcription and chromatin remodeling. These processes are coordinated to maintain genome integrity and ensure accurate duplication of genetic and epigenetic information. Genome-wide studies have provided evidence of the relationship between transcription and DNA replication timing. A global analysis of DNA replication initiation in T. brucei showed that TbORC1 (subunit of the origin recognition complex, ORC) binding sites are located at the boundaries of transcription units. Although recent studies in T. brucei indicate functional links among DNA replication and transcription, the underlying mechanisms remain unknown. In this study, we adapted …


Interactions Between The Organellar Pol1a, Pol1b, And Twinkle Dna Replication Proteins And Their Role In Plant Organelle Dna Replication, Stewart Anthony Morley Mar 2019

Interactions Between The Organellar Pol1a, Pol1b, And Twinkle Dna Replication Proteins And Their Role In Plant Organelle Dna Replication, Stewart Anthony Morley

Theses and Dissertations

Plants maintain organelle genomes that are descended from ancient microbes. Ages ago, these ancient microbes were engulfed by larger cells, beginning a process of co-evolution we now call the endo-symbiotic theory. Over time, DNA from the engulfed microbe was transferred to the genome of the larger engulfing cell, eventually losing the ability to be free-living, and establishing a permanent residency in the larger cell. Similarly, the larger cell came to rely so much on the microbe it had engulfed, that it too lost its ability to survive without it. Thus, mitochondria and plastids were born. Nearly all multicellular eukaryotes possess …


Functional Analysis Of The Replication Fork Proteome Identifies Bet Proteins As Pcna Regulators, Sarah R. Wessel, Kareem N. Mohni, Jessica W. Luzwick, Huzefa Dungrawala, David Cortez Jan 2019

Functional Analysis Of The Replication Fork Proteome Identifies Bet Proteins As Pcna Regulators, Sarah R. Wessel, Kareem N. Mohni, Jessica W. Luzwick, Huzefa Dungrawala, David Cortez

Molecular Biosciences Faculty Publications

Identifying proteins that function at replication forks is essential to understanding DNA replication, chromatin assembly, and replication-coupled DNA repair mechanisms. Combining quantitative mass spectrometry in multiple cell types with stringent statistical cutoffs, we generated a high-confidence catalog of 593 proteins that are enriched at replication forks and nascent chromatin. Loss-of-function genetic analyses indicate that 85% yield phenotypes that are consistent with activities in DNA and chromatin replication or already have described functions in these processes. We illustrate the value of this resource by identifying activities of the BET family proteins BRD2, BRD3, and BRD4 in controlling DNA replication. These proteins …