Ku recruits XLF to DNA double-strand breaks

Ken Ichi Yano, Keiko Morotomi-Yano, Shih Ya Wang, Naoya Uematsu, Kyung Jong Lee, Aroumougame Asaithamby, Eric Weterings, David J. Chen

Research output: Contribution to journalArticle

132 Scopus citations

Abstract

XRCC4-like factor (XLF)-also known as Cernunnos-has recently been shown to be involved in non-homologous end-joining (NHEJ), which is the main pathway for the repair of DNA double-strand breaks (DSBs) in mammalian cells. XLF is likely to enhance NHEJ by stimulating XRCC4-ligase IV-mediated joining of DSBs. Here, we report mechanistic details of XLF recruitment to DSBs. Live cell imaging combined with laser micro-irradiation showed that XLF is an early responder to DSBs and that Ku is essential for XLF recruitment to DSBs. Biochemical analysis showed that Ku-XLF interaction occurs on DNA and that Ku stimulates XLF binding to DNA. Unexpectedly, XRCC4 is dispensable for XLF recruitment to DSBs, although photobleaching analysis showed that XRCC4 stabilizes the binding of XLF to DSBs. Our observations showed the direct involvement of XLF in the dynamic assembly of the NHEJ machinery and provide mechanistic insights into DSB recognition.

Original languageEnglish (US)
Pages (from-to)91-96
Number of pages6
JournalEMBO Reports
Volume9
Issue number1
DOIs
StatePublished - Jan 2008

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics

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    Yano, K. I., Morotomi-Yano, K., Wang, S. Y., Uematsu, N., Lee, K. J., Asaithamby, A., Weterings, E., & Chen, D. J. (2008). Ku recruits XLF to DNA double-strand breaks. EMBO Reports, 9(1), 91-96. https://doi.org/10.1038/sj.embor.7401137