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Determination Of The Atomic Resolution Structure Of A Dna Polymerase I Isolated From Rhodothermus Marinus, Natalie S. Omattage
Determination Of The Atomic Resolution Structure Of A Dna Polymerase I Isolated From Rhodothermus Marinus, Natalie S. Omattage
Honors Theses
DNA polymerase I employs a multistep mechanism for sorting correctly paired nucleotides from mismatches. We aim to characterize reaction intermediates during nucleotide selection to better understand how this class of enzymes achieves high DNA replication fidelity. DNA polymerase I from R. marinus contains an unusual and disruptive proline in the mobile O helix near the active site. To characterize this enzyme, the structure of the large (5´-to-3´ exo-deficient) fragment of the R. marinus DNA polymerase I (RF) was solved to 2.95 Å (R = 0.234) using multi-wavelength anomalous dispersion. Alignment …
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). …