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Full-Text Articles in Molecular Biology

Centromere Identity And The Nature Of The Cenp-A-Containing Nucleosome, Samantha Jane Falk Jan 2016

Centromere Identity And The Nature Of The Cenp-A-Containing Nucleosome, Samantha Jane Falk

Publicly Accessible Penn Dissertations

The centromere is an essential chromosomal locus that serves as the site of kinetochore formation, ensuring accurate chromosome segregation during mitosis and meiosis. While most centromeres form on repetitive DNA, the underlying DNA sequence is neither necessary nor sufficient to support centromere function, suggesting that this locus is epigenetically defined. The histone H3 variant centromere protein A (CENP-A) replaces H3 in nucleosomes at the centromere and is the best candidate to provide this epigenetic mark. This thesis aims to understand the features of the CENP-A nucleosome that impart its ability to mark and stabilize functional centromeres. In the first part ...


The Regulation Of Psf Activity In T Cells By Trap150 And Gsk3, Christopher Yarosh Jan 2016

The Regulation Of Psf Activity In T Cells By Trap150 And Gsk3, Christopher Yarosh

Publicly Accessible Penn Dissertations

PSF is a ubiquitously expressed and essential nuclear protein that influences many aspects of the genome maintenance and gene expression pathways. Although previous studies have identified numerous protein cofactors and nucleic acid targets of PSF, insufficient work has been done to understand how it is regulated to accomplish its various functions in a coordinated manner. Previous research in the Lynch laboratory demonstrated that, in T cells, PSF is a downstream target of the serine/threonine kinase GSK3. Phosphorylation of PSF T687 by GSK3 promotes interaction of PSF with another multifunctional nuclear factor, TRAP150. This interaction prevents PSF from binding RNA ...


Potentiated Hsp104 Variants Suppress The Toxicity Of Most Overexpressed Dosage-Sensitive Yeast Genes, Michael Yancey Soo Jan 2016

Potentiated Hsp104 Variants Suppress The Toxicity Of Most Overexpressed Dosage-Sensitive Yeast Genes, Michael Yancey Soo

Publicly Accessible Penn Dissertations

Maintenance of optimal gene expression levels is critical for cell viability and homeostasis. However, misregulation of gene expression can and regularly occur. One type of detrimental misregulation involves overexpression of a single gene that can cause organismal death is dosage sensitivity, which is often due to increased concentration of the protein encoded by the gene. Deleterious increases in the expression of specific proteins are associated with various neurodegenerative diseases such as Parkinson’s and Alzheimer’s Diseases as well as other cellular maladies including various cancers and Down Syndrome. In yeast, it has been estimated that ~20% of genes are ...


Deciphering The Tetrad Of Epigenetic Cytosine Modifications, Monica Yun Liu Jan 2016

Deciphering The Tetrad Of Epigenetic Cytosine Modifications, Monica Yun Liu

Publicly Accessible Penn Dissertations

A tetrad of epigenetic cytosine modifications imbues the DNA code with complex, dynamic meaning. DNA methyltransferase enzymes deposit methyl marks on the 5-carbon of cytosine, forming 5-methylcytosine (mC), which generally mediates long-term, locus-specific transcriptional repression during development and reprogramming. Ten-eleven translocation (TET) family enzymes oxidize the methyl group in three steps, forming predominantly 5-hydroxymethylcytosine (hmC) but also low levels of 5-formylcytosine (fC) and 5-carboxylcytosine (caC). These additional bases likely provide pathways for erasing methylation, but they may also harbor epigenetic functions in their own right. Questions regarding how each base forms and functions drive at the fundamental biology of the ...