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Novel Redox And Dna-Dependent Conformational Changes In Human Ku, A Dna-Double Strand Break Repair Protein, Jason Alexander Lehman
Novel Redox And Dna-Dependent Conformational Changes In Human Ku, A Dna-Double Strand Break Repair Protein, Jason Alexander Lehman
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Ionizing radiation (IR) and radiomimetic drugs used in cancer chemotherapy cause DNA double-strand breaks which are repaired by the nonhomologous end joining (NHEJ) pathway. Ku is a heterodimeric protein comprised of 70 and 80 kDa subunits and recognizes free DNA ends. Once Ku is bound to DNA, it binds to the DNA-dependent protein kinase catalytic subunit (DNA-PKcs), and forms a heterotrimeric DNA-PK complex for repair and damage signaling.
We have analyzed the Ku protein using multiple biochemical techniques and uncovered a novel reversible redox change (Andrews, Lehman and Turchi, (2006) JBC 281(19):13596-603). From this data, we hypothesized that a redox-dependent …