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The Mechanism Of Mitochondrial Folate Transport By The Mitochondrial Folate Transporter, Scott Alan Lawrence
The Mechanism Of Mitochondrial Folate Transport By The Mitochondrial Folate Transporter, Scott Alan Lawrence
Theses and Dissertations
The mitochondrial folate transport protein (MFT) functions to transport folates into the mitochondrial matrix. The MFT is a member of a mitochondrial carrier family (MCF) of proteins that have a high degree of sequence and structural similarities, yet they transport vastly different substrates at high specificities. In this dissertation research, the folate-specific transport mechanism of the MFT was explored using experimental and computational techniques. MFT residues that differed from MCF consensus residues in conserved PxD/ExxK/R motifs and at a predicted substrate-binding site common to all MCF proteins were investigated. Site-directed mutagenesis of these anomalous residues in the MFT revealed that …
Action Of Tyrosyl Dna Phosphodiesterase On 3'-Phosphoglycolate Terminated Dna Strand Breaks, Haritha Tatavarthi
Action Of Tyrosyl Dna Phosphodiesterase On 3'-Phosphoglycolate Terminated Dna Strand Breaks, Haritha Tatavarthi
Theses and Dissertations
Free radical-mediated DNA double strand breaks (DSBs) are induced either directly by ionizing radiation or by certain chemicals like bleomycin. These breaks are terminated by 3'-PG (PO4CH2COOˉ) or 3'-phosphate groups formed as a result of fragmentation of deoxyribose. To study the nature of repair of these 3'-blocked breaks, we constructed substrates mimicking free-radical induced DSBs. Human and yeast tyrosyl DNA-phosphodiesterase (Tdpl) efficiently processed substrates with 3'-PGs, in either the presence or absence of magnesium, to give a 3'-phosphate. Gel filtration chromatography and western blotting codmed that the putative enzyme in human extracts that efficiently processed PG was indeed tyrosyl DNA-phosphodiesterase. …