Ku DNA end-binding protein modulates homologous repair of double-strand breaks in mammalian cells

A. J. Pierce, P. Hu, M. Han, N. Ellis, M. Jasin

Research output: Contribution to journalArticle

373 Scopus citations

Abstract

Chromosomal double-strand breaks (DSBs) in mammalian cells are repaired by either homology-directed repair (HDR), using a homologous sequence as a repair template, or nonhomologous end-joining (NHEJ), which often involves sequence alterations at the DSB site. To characterize the interrelationship of these two pathways, we analyzed HDR of a DSB in cells deficient for NHEJ components. We find that the HDR frequency is enhanced in Ku70-/-, XRCC4-/-, and DNA-PKcs-/- cells, with the increase being particularly striking in Ku70-/- cells. Neither sister-chromatid exchange nor gene-targeting frequencies show a dependence on these NHEJ proteins. A Ku-modulated two-ended versus one-ended chromosome break model is presented to explain these results.

Original languageEnglish (US)
Pages (from-to)3237-3242
Number of pages6
JournalGenes and Development
Volume15
Issue number24
DOIs
StatePublished - Dec 15 2001

Keywords

  • DNA double-strand break
  • DNA-PK
  • Gene targeting
  • Homologous recombination
  • Ku protein
  • Nonhomologous end-joining
  • Sister-chromatid exchange

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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