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

   


Authors: Pierce, A. J.; Hu, P.; Han, M.; Ellis, N.; Jasin, M.
Article Title: Ku DNA end-binding protein modulates homologous repair of double-strand breaks in mammalian cells
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.
Keywords: controlled study; gene mutation; sequence analysis; mutation; dna-binding proteins; nonhuman; binding affinity; polymerase chain reaction; animal cell; mouse; mammalia; animals; mice; mice, knockout; dna damage; homologous recombination; gene targeting; dna repair; sister chromatid; cell line; protein binding; gene frequency; animalia; transcription factors; dna strand breakage; nuclear proteins; cloning, molecular; dna; double stranded dna; genetic transfection; recombination, genetic; sister chromatid exchange; binding site; dna primers; sequence homology; ku antigen; dna helicases; mammal cell; dna fragment; modulation; dna-pk; dna-activated protein kinase; nonhomologous end-joining; antigens, nuclear; sister-chromatid exchange; binding kinetics; dna double-strand break; humans; priority journal; article; ku protein; chromatid exchange
Journal Title: Genes and Development
Volume: 15
Issue: 24
ISSN: 0890-9369
Publisher: Cold Spring Harbor Laboratory Press  
Date Published: 2001-12-15
Start Page: 3237
End Page: 3242
Language: English
DOI: 10.1101/gad.946401
PUBMED: 11751629
PROVIDER: scopus
PMCID: PMC312854
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-0035893363&partnerID=40&md5=12ba8547a5081be32f4f752d6009ce45
Notes: Export Date: 21 May 2015 -- Source: Scopus
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MSK Authors
  1. Peng Hu
    7 Hu
  2. Andrew J Pierce
    11 Pierce
  3. Nathan A Ellis
    74 Ellis
  4. Maria Jasin
    249 Jasin
  5. Mingguang Han
    5 Han
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