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Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Dna Polymerase Θ (Polq) And The Cellular Defense Against Dna Damage, Matthew J. Yousefzadeh May 2015

Dna Polymerase Θ (Polq) And The Cellular Defense Against Dna Damage, Matthew J. Yousefzadeh

UT GSBS Dissertations and Theses (Open Access)

In mammalian cells, DNA polymerase θ (POLQ) is an unusual specialized DNA polymerase whose in vivo function is under active investigation. The protein is comprised of an N-terminal helicase-like domain, a C-terminal DNA polymerase domain, and a large central domain that spans between the two. This arrangement is also found in the Drosophila Mus308 protein, which helps confer resistance to DNA interstrand crosslinking agents. Homologs of POLQ and Mus308 are found in eukaryotes, including plants, but a comparison of phenotypes suggests that not all of these genes are functional orthologs. Flies with defective Mus308 are sensitive to DNA interstrand crosslinking ...


Translesion Synthesis And Mutations: On The Mutagenic Properties Of The Two Dna Lesions, 8-Oxo-G And Pt-Gg, And The Functions Of Y-Family Dna Polymerases And Rev3l On The Bypass Of Each Of The Dna Lesions In Mammalian Cells, Lizhen Guo Apr 2015

Translesion Synthesis And Mutations: On The Mutagenic Properties Of The Two Dna Lesions, 8-Oxo-G And Pt-Gg, And The Functions Of Y-Family Dna Polymerases And Rev3l On The Bypass Of Each Of The Dna Lesions In Mammalian Cells, Lizhen Guo

Electronic Thesis and Dissertation Repository

I studied the capabilities of the two DNA lesions 8-oxo-guanine and cisplatin intrastrand crosslinked 1,2-d(GpG) or Pt-GG to cause mutations in mammalian cells. Using isogenic cell lines generated from mice with selective gene knockouts of distinct DNA polymerases as models, I deduced the biological functions of the translesion DNA polymerases Pol eta, Pol kappa, Pol iota, Rev1 and Rev3L on bypassing each of the lesions 8-oxo-G and Pt-GG. My study takes advantage of the Next Generation Sequencing (NGS) technology to determine mutagenic effects of the DNA lesions in vivo and effects of translesion DNA polymerases on bypassing the ...


Crystallization And Preliminary X-Ray Analysis Of The Plasmodium Falciparum Apicoplast Dna Polymerase, Morgan Eilise Milton, Jun-Yong Choe, Richard B. Honzatko, Scott W. Nelson Mar 2015

Crystallization And Preliminary X-Ray Analysis Of The Plasmodium Falciparum Apicoplast Dna Polymerase, Morgan Eilise Milton, Jun-Yong Choe, Richard B. Honzatko, Scott W. Nelson

Biochemistry, Biophysics and Molecular Biology Publications

Infection by the parasite Plasmodium falciparum is the leading cause of malaria in humans. The parasite has a unique and essential plastid-like organelle called the apicoplast. The apicoplast contains a genome that undergoes replication and repair through the action of a replicative polymerase (apPOL). apPOL has no direct orthologs in mammalian polymerases and is therefore an attractive antimalarial drug target. No structural information exists for apPOL, and the Klenow fragment of Escherichia coli DNA polymerase I, which is its closest structural homolog, shares only 28% sequence identity. Here, conditions for the crystallization of and preliminary X-ray diffraction data from crystals ...


Fidelity, Mismatch Extension, And Proofreading Activity Of The Plasmodium Falciparum Apicoplast Dna Polymerase, Bentley Wingert, Eric Evan Parrott, Scott W. Nelson Oct 2013

Fidelity, Mismatch Extension, And Proofreading Activity Of The Plasmodium Falciparum Apicoplast Dna Polymerase, Bentley Wingert, Eric Evan Parrott, Scott W. Nelson

Biochemistry, Biophysics and Molecular Biology Publications

Plasmodium falciparum, a parasitic organism and one of the causative agents of malaria, contains an unusual organelle called the apicoplast. The apicoplast is a nonphotosynthetic plastid responsible for supplying the parasite with isoprenoid units and is therefore indispensable. Like mitochondria and the chloroplast, the apicoplast contains its own genome and harbors the enzymes responsible for its replication. In this report, we determine the relative probabilities of nucleotide misincorporation by the apicoplast polymerase (apPOL), examine the kinetics and sequence dependence of mismatch extension, and determine the rates of mismatch removal by the 3′ to 5′ proofreading activity of the DNA polymerase ...


Substrate Recognition By The Yeast Rev1 Protein And Dna Polymerase Ζ, Craig A Howell Jan 2008

Substrate Recognition By The Yeast Rev1 Protein And Dna Polymerase Ζ, Craig A Howell

Theses and Dissertations

DNA damage blocks replication by classical DNA polymerases, those that replicate nondamaged DNA during normal DNA replication and repair, by altering the geometry of the DNA. Consequently, translesion synthesis, the replication of damaged DNA, is catalyzed by non-classical DNA polymerases, which are capable of accommodating the inherent distorted geometry of damaged DNA.

The yeast Rev1 protein (Rev1p) specifically catalyzes the incorporation of cytosine opposite template guanine and several types of DNA damage utilizing a unique mechanism of nucleotide selection whereby the sidechain of Arg-324 acts as the template by forming hydrogen bonds with the incoming cytosine. To better understand the ...