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

  • He D
  • Lee S
  • Hendrickson E
  • 4

    Readers

    Mendeley users who have this article in their library.
  • 28

    Citations

    Citations of this article.

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.

Author-supplied keywords

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

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

  • Dong Ming He

  • Sang Eun Lee

  • Eric A. Hendrickson

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free