Ku recruits XLF to DNA double-strand breaks

被引：139

作者：

Yano, Ken-ichi ^{[1
]}

Morotomi-Yano, Keiko ^{[1
]}

Wang, Shih-Ya ^{[1
]}

Uematsu, Naoya ^{[1
]}

Lee, Kyung-Jong ^{[1
]}

Asaithamby, Aroumougame ^{[1
]}

Weterings, Eric ^{[1
]}

Chen, David J. ^{[1
]}

机构：

[1] Univ Texas SW Med Ctr Dallas, Dept Radiat Oncol, Div Mol Radiat Biol, Dallas, TX 75390 USA

来源：

EMBO REPORTS | 2008年 / 9卷 / 01期

关键词：

Cernunnos; ku; non-homologous end-joining; XLF; XRCC4;

D O I：

10.1038/sj.embor.7401137

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 photo-bleaching 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.

引用

页码：91 / 96

页数：6

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