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

Dong Ming He, Sang Eun Lee, Eric A. Hendrickson

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28 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)43-56
Number of pages14
JournalMutation Research - DNA Repair
Volume363
Issue number1
DOIs
StatePublished - May 15 1996

Keywords

  • DNA double-strand break repair
  • Ku
  • V(D)J recombination mutant
  • X-ray sensitivity

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