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Full-Text Articles in Life Sciences
Kinetic Characterization Of Two C-Family Polymerases From The Gram-Positive Bacterium Staphylococcus Aureus, Sean P. Fagan
Kinetic Characterization Of Two C-Family Polymerases From The Gram-Positive Bacterium Staphylococcus Aureus, Sean P. Fagan
Legacy Theses & Dissertations (2009 - 2024)
In this dissertation, I review the fundamental processes and mechanisms for bacterial DNA replication, especially the mechanisms employed by high-fidelity DNA polymerases to replicate the genome. Unlike the prototypical bacterial system from Escherichia coli which uses a single C-family polymerase, DNA polymerase IIIα (Pol IIIα), to replicate the genome, low-GC content Gram-positive bacteria utilize two essential C-family polymerases, PolC and DnaE. PolC and DnaE work cooperatively to replicate the genome, with DnaE initiating synthesis from RNA-primers and PolC performing the bulk synthesis. Although atomic structures of both PolC and Pol IIIα are available, detailed pre-steady state kinetic analysis of the …
Pre-Steady-State Kinetic Characterization Of An Antibiotic-Resistant Mutation Of Staphylococcus Aureus Polc, Rachel Alice Nelson
Pre-Steady-State Kinetic Characterization Of An Antibiotic-Resistant Mutation Of Staphylococcus Aureus Polc, Rachel Alice Nelson
Legacy Theses & Dissertations (2009 - 2024)
In this dissertation I provide a pre-steady-state kinetic characterization of an antibiotic-resistant mutant of a Staphylococcus aureus DNA polymerase. Staphylococcus aureus is one of the most common causes of infections in humans, and is widely known for its ability to acquire resistance to most antibiotics. Staphylococci infections pose a significant burden to the healthcare system and increase mortality, as more than 95% of Methicillin-Resistant S. aureus (MRSA) infections do not respond to first-line antibiotics. The limited treatment options for Staphylococci infections underscores the need for novel, alternative strategies. In this thesis, I discuss 6-anilinouracils (6-AU), a family of potent dGTP …
Mechanisms Of Dna Synthesis And Fidelity By Y-Family Translesion And C-Family Replicative Polymerases, Purba Mukherjee
Mechanisms Of Dna Synthesis And Fidelity By Y-Family Translesion And C-Family Replicative Polymerases, Purba Mukherjee
Legacy Theses & Dissertations (2009 - 2024)
Since the discovery of the DNA polymerase by Arthur Kornberg nearly 60 years ago, there have been great advances in understanding the involvement of polymerases in replication and repair. Years of genetic, biochemical and structural studies have lead to the classification of DNA-dependent DNA polymerases into six families: A, B, C, D, X and Y. In this work, I have focussed on two different families, C and Y. Hence this work is divided into two parts. Part one discusses the studies on Y-family polymerases. All Y-family polymerases are involved in replicating past DNA lesions. The ability to tolerate unnatural nucleotides …
Mechanistic Studies Of C- And Y-Family Dna Polymerases, Indrajit Lahiri
Mechanistic Studies Of C- And Y-Family Dna Polymerases, Indrajit Lahiri
Legacy Theses & Dissertations (2009 - 2024)
DISSERTATION ABSTRACT
Y-Family Dna Polymerases : Mechanism Of Single-Base Deletion And Effect Of Pcna Interaction, Yifeng Wu
Y-Family Dna Polymerases : Mechanism Of Single-Base Deletion And Effect Of Pcna Interaction, Yifeng Wu
Legacy Theses & Dissertations (2009 - 2024)
Translesional synthesis (TLS) by specialized Y-family DNA polymerases is a DNA damage tolerance pathway to bypass DNA lesions that have not been repaired by other DNA repair mechanisms. Despite their valuable lesion bypass ability, the Y-family DNA polymerases display a much lower fidelity upon replicating undamaged DNA. Their activity therefore needs to be well regulated in the cell. In our first project, we examined how an archaeal Y-family DNA polymerase, Dpo4, makes single-base deletions during replication. Dpo4 belongs to the DinB subfamily which is known to make single-base deletions. Although previous studies suggested that it uses a dNTP-stabilized misalignment mechanism, …
Dna Repair Fidelity And Cancer : Structural And Kinetic Insights From Dna Polymerase Beta Mutator Variants, Chelsea Lynne Gridley
Dna Repair Fidelity And Cancer : Structural And Kinetic Insights From Dna Polymerase Beta Mutator Variants, Chelsea Lynne Gridley
Legacy Theses & Dissertations (2009 - 2024)
DNA polymerases are essential for genome replication and DNA repair in all living organisms. Precise DNA replication is critical for the preservation of genomic stability. Any insult, endogenous/exogenous, to cellular DNA requires properly functioning repair polymerases. In eukaryotes, DNA polymerase beta, a small enzyme (39 kDa), plays an important role in DNA repair during the base excision repair pathway. Pol beta catalyzes the incorporation of nucleotides in small stretches (1-6 nucleotides) of damaged double-stranded DNA. Should gap-filling synthesis by pol beta be compromised, mutations in genomic DNA accumulate, which are frequently linked to human diseases, including cancers. For this reason, …
Structural And Functional Characterization Of Dna Polymerase Ss Mutator Mutants, Sneha Rangarajan
Structural And Functional Characterization Of Dna Polymerase Ss Mutator Mutants, Sneha Rangarajan
Legacy Theses & Dissertations (2009 - 2024)
DNA Polymerase ß (polß) plays a crucial role in repairing damaged DNA in a process called Base Excision Repair (BER). BER is a major pathway of DNA repair, making this system absolutely vital for maintaining genomic integrity. Recent studies estimate 30% of human tumors to contain polß variants that led us to believe that there is a high degree of association between mutations in polß and cancer. In this pathway, after recognition and excision of the damaged base, the DNA is cleaved at an apurinic (AP) site by AP endonuclease leaving behind a 3' hydroxyl and 5' deoxyribose phosphate (dRP). …