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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 …
Assessing The Role Of Ku70 Vwa Domain Phosphorylation In The Inhibition Of Aurora B And Activation Of The Dna Damage Response, Elizabeth A. Walden
Assessing The Role Of Ku70 Vwa Domain Phosphorylation In The Inhibition Of Aurora B And Activation Of The Dna Damage Response, Elizabeth A. Walden
Electronic Thesis and Dissertation Repository
Ku is a key component of the Non-Homologous End Joining DNA repair pathway. Recently, a function for Ku in DNA damage response (DDR) signalling was identified through studies exploring a Ku70 S155D phosphomimetic mutant. We hypothesize that Ku70 S155D mimics phosphorylation of Ku70 in response to DNA damage, and that Ku S155 phosphorylation inhibits Aurora B and causes sustained DDR activation. In this study we show that the S155D mutant is competent for heterodimerization, and its expression does not induce DNA damage. Phosphorylated Ku70 associates with Aurora B by co-immunoprecipitation and this association was demonstrated in situ with Ku70 S155D. …