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Full-Text Articles in Biochemistry, Biophysics, and Structural Biology
Structural And Functional Characterization Of Non-Homologous End Joining Factors, Huasheng Wang
Structural And Functional Characterization Of Non-Homologous End Joining Factors, Huasheng Wang
Electronic Thesis and Dissertation Repository
DNA double strand breaks represent the most toxic form of DNA damage. In mammals, non-homologous end-joining (NHEJ) is the primary DNA repair pathway for such damage, preventing both carcinogenesis and accelerated aging. Structural understanding of this repair pathway has received considerable attention, but has been significantly limited by the inability to obtain structures of higher order nucleoprotein complexes. A main obstacle in this respect has been difficulty in obtaining highly purified proteins, sufficient for structural determination. Improved protein expression and purification methods developed in this thesis permitted several NHEJ complexes to be selected for structural studies. Among these, Ku70-DNA and …
Autoinhibition And Activation Of Parkin, Jacob D. Aguirre
Autoinhibition And Activation Of Parkin, Jacob D. Aguirre
Electronic Thesis and Dissertation Repository
Mutations in the gene encoding parkin, an E3-ubiquitin ligase, result in 50% of Autosomal Recessive Juvenile Parkinsonism cases. Parkin has been identified as a key mediator of mitochondrial regeneration following oxidative stress, and pathogenic mutations have been shown to impair its ubiquitin ligase activity. Neurodegeneration of dopamine-producing neurons appears to be a downstream consequence of parkin loss-of-function, resulting in early-onset forms of Parkinson’s disease. Although ubiquitination activity is essential for its neuroprotective function, parkin is autoinhibited in its native state by various mechanisms, including its N-terminal ubiquitin-like (UBL) domain. Therefore, the overarching objective of this thesis was to structurally characterize …