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You searched for id:"oai:d-scholarship.pitt.edu:32997". One record found.

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1. Kong, Muwen. SINGLE-MOLECULE STUDIES OF RAD4-RAD23 REVEAL A DYNAMIC DNA DAMAGE RECOGNITION PROCESS.

Degree: 2017, University of Pittsburgh

Nucleotide excision repair (NER) is an evolutionarily conserved mechanism that processes helix-destabilizing and/or -distorting DNA lesions, such as UV-induced photoproducts. As the first step towards productive repair, the human NER damage sensor XPC-RAD23B needs to efficiently locate sites of damage among billons of base pairs of undamaged DNA. In this dissertation, we investigated the dynamic protein-DNA interactions during the damage recognition step using a combination of fluorescence-based single-molecule DNA tightrope assays, atomic force microscopy, as well as cell survival and in vivo repair kinetics assays. We observed that quantum dot-labeled Rad4-Rad23, the yeast homolog of human XPC-RAD23B, formed nonmotile complexes on DNA or conducted a one-dimensional search via either random diffusion or constrained motion along DNA. Using atomic force microscopy, we studied binding of Rad4 lacking the β-hairpin domain 3 (BHD3) to damage-containing DNA and found that this structural motif is non-essential for damage-specific binding or DNA bending. Furthermore, we demonstrated that deletion of seven residues in the tip of β-hairpin in BHD3 increased Rad4-Rad23 constrained motion at the expense of stable binding at sites of DNA lesions, without diminishing cellular UV resistance or photoproduct repair in vivo. These results suggest a distinct intermediate in the damage recognition process during NER, allowing dynamic DNA damage detection at a distance. Finally, we explore existing physical models and examples of subdiffusive motion, and discuss a model in which constrained motion by Rad4-Rad23 on DNA may be driven by conformational changes of the protein.

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APA (6th Edition):

Kong, M. (2017). SINGLE-MOLECULE STUDIES OF RAD4-RAD23 REVEAL A DYNAMIC DNA DAMAGE RECOGNITION PROCESS. (Thesis). University of Pittsburgh. Retrieved from http://d-scholarship.pitt.edu/32997/1/Thesis_FIN_080717.pdf ; http://d-scholarship.pitt.edu/32997/

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Kong, Muwen. “SINGLE-MOLECULE STUDIES OF RAD4-RAD23 REVEAL A DYNAMIC DNA DAMAGE RECOGNITION PROCESS.” 2017. Thesis, University of Pittsburgh. Accessed October 24, 2017. http://d-scholarship.pitt.edu/32997/1/Thesis_FIN_080717.pdf ; http://d-scholarship.pitt.edu/32997/.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Kong, Muwen. “SINGLE-MOLECULE STUDIES OF RAD4-RAD23 REVEAL A DYNAMIC DNA DAMAGE RECOGNITION PROCESS.” 2017. Web. 24 Oct 2017.

Vancouver:

Kong M. SINGLE-MOLECULE STUDIES OF RAD4-RAD23 REVEAL A DYNAMIC DNA DAMAGE RECOGNITION PROCESS. [Internet] [Thesis]. University of Pittsburgh; 2017. [cited 2017 Oct 24]. Available from: http://d-scholarship.pitt.edu/32997/1/Thesis_FIN_080717.pdf ; http://d-scholarship.pitt.edu/32997/.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Kong M. SINGLE-MOLECULE STUDIES OF RAD4-RAD23 REVEAL A DYNAMIC DNA DAMAGE RECOGNITION PROCESS. [Thesis]. University of Pittsburgh; 2017. Available from: http://d-scholarship.pitt.edu/32997/1/Thesis_FIN_080717.pdf ; http://d-scholarship.pitt.edu/32997/

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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