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Production de domaines recombinants PRODH en vue de l'analyse structurale & Caractérisation de la région 51-160 de la protéine KIN17 humaine par RMN et Modélisation Moléculaire

Abstract : Maintenance of the genomic integrity is crucial for all living organisms. Since cells are continuously submitted to genotoxic stresses that induce DNA damages, they have evolved sophisticated mechanisms to detect, signal the presence of, and repair these lesions. Among sources of DNA damage, UV radiation alters DNA structure and can cause mutations and chromosomal translocations. In humans, Nucleotide Excision Repair (NER) is an efficient way to remove DNA lesions induced by UV or ionizing radiation. NER inactivation leads to cell death and increase the susceptibility to develop diseases such as cancer and hereditary disorders. Among numerous proteins involved in the NER pathway, XPA and XPC can trigger the expression of several secondary genes such as KIN17 which encodes a 45 kDa protein. In order to elucidate the biological function of KIN17, biochemical and structural studies of its domains were performed. This thesis work focus on the region 51-160 of the human protein. NMR and Molecular Modelling studies showed that this region adopts a winged helix fold mainly know for its ability to bind nucleic acids. However, structure-activity relationships revealed that the Winged Helix of human KIN17 is not able to bind DNA or RNA. On the other hand, this domain exhibits a highly conserved surface involved in intramolecular interactions with the N-terminal region of the protein.
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https://tel.archives-ouvertes.fr/tel-00124229
Contributor : Ludovic Carlier <>
Submitted on : Friday, January 12, 2007 - 3:46:45 PM
Last modification on : Tuesday, February 5, 2019 - 11:44:10 AM
Long-term archiving on: : Tuesday, April 6, 2010 - 7:52:46 PM

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  • HAL Id : tel-00124229, version 1

Citation

Ludovic Carlier. Production de domaines recombinants PRODH en vue de l'analyse structurale & Caractérisation de la région 51-160 de la protéine KIN17 humaine par RMN et Modélisation Moléculaire. Biophysique [physics.bio-ph]. Université de Rouen, 2006. Français. ⟨tel-00124229⟩

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