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Crystallographic Studies of DNA Replication and Repair Proteins

Tomanicek, Stephen Joseph
http://rave.ohiolink.edu/etdc/view?acc_num=toledo1115325888

Abstract Details

2005, Doctor of Philosophy, University of Toledo, Chemistry.
The duplication of genomic information is central to the survival of organisms in all kingdoms of life. DNA replication and repair processes are essential for maintaining the fidelity and genomic stability required for life. Many proteins are involved directly in a number of coordinated interactions to ensure the accurate and efficient replication and repair of DNA. However, a number of these coordinated interactions during the replication and repair of DNA remain uncharacterized. Therefore, studying the nature of the various protein protein and protein substrate interactions can provide a more comprehensive understanding of both DNA replication and repair in all forms of life. Specifically, the fidelity of DNA replication is highly dependent on the function of the flap endonuclease (FEN 1) family of enzymes. The FEN-1 family of DNA replication associated DNA repair enzymes are structure specific 5’ to 3’ endonucleases that are members of the RAD2/RAD27 family of eukaryotic nucleases. The FEN 1 family of enzymes are also functionally related to both the bacteriophage and prokaryotic 5’ to 3’ exonucleases. Many of the enzymes in the RAD2/RAD27 family of nucleases are involved in the processing of Okazaki fragment primers during lagging-strand DNA synthesis and in processing strands displaced during DNA synthesis associated with repair. However, a comprehensive structural characterization of the structure specific substrate recognition of the FEN 1 family of enzymes has not yet been completed. This work was focused primarily on structural studies of the archaeal Aeropyrum pernix (Ape) FEN-1 enzyme and the T4 RNase H, a FEN 1 homologue in the bacteriophage T4. A number of X ray crystallographic studies were focused on understanding the molecular basis of nucleic acid substrate recognition and the role of divalent metal ions in the catalytic mechanism of these enzymes. These structural studies have provided a more complete understanding of how catalysis is facilitated by the structure specific substrate recognition of these essential enzymes in both DNA replication and repair.
Timothy Mueser (Advisor)
245 p.
Chemistry, Biochemistry
flap endonuclease-1; FEN-1

Recommended Citations

Citations

  • Tomanicek, S. J. (2005). Crystallographic Studies of DNA Replication and Repair Proteins [Doctoral dissertation, University of Toledo]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1115325888

    APA Style (7th edition)

  • Tomanicek, Stephen. Crystallographic Studies of DNA Replication and Repair Proteins. 2005. University of Toledo, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=toledo1115325888.

    MLA Style (8th edition)

  • Tomanicek, Stephen. "Crystallographic Studies of DNA Replication and Repair Proteins." Doctoral dissertation, University of Toledo, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1115325888

    Chicago Manual of Style (17th edition)

toledo1115325888
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© 2005, all rights reserved.
This open access ETD is published by University of Toledo and OhioLINK.