Restoration of X-ray and etoposide resistance, Ku-end binding activity and V(D)J recombination to the Chinese hamster sxi-3 mutant by a hamster Ku86 cDNA

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Abstract

Ku is a heterodimeric protein composed of 86 and 70 kDa subunits that binds preferentially to the double-stranded ends of DNA. Recent molecular characterization of ionizing-radiation sensitive (IR(s)) mutants belonging to the XRCC5 complementation group demonstrated the involvement of Ku in DNA double-strand break (DSB) repair and lymphoid V(D)J recombination. Here, we describe the isolation of a full-length hamster cDNA encoding the large subunit of the Ku heterodimer and demonstrate that the stable expression of this cDNA can functionally restore IR(r), Ku DNA end-binding activity and V(D)J recombination proficiency in the Chinese hamster IR(s) sxi-3 mutant. Moreover, we also demonstrate that sxi-3 cells are hypersensitive to etoposide, a DNA topoisomerase II inhibitor, and that resistance to this drug was restored by the Ku86 cDNA. These experiments suggest that a defect in the large subunit of the heterodimeric Ku protein is the sole factor responsible for the known defects of sxi-3 cells and our data further support the role of Ku in DNA DSB repair and V(D)J recombination.

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He, D. M., Lee, S. E., & Hendrickson, E. A. (1996). Restoration of X-ray and etoposide resistance, Ku-end binding activity and V(D)J recombination to the Chinese hamster sxi-3 mutant by a hamster Ku86 cDNA. Mutation Research - DNA Repair, 363(1), 43–56. https://doi.org/10.1016/0921-8777(95)00060-7

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