title: Functional significance of the interaction with Ku in DNA double-strand break recognition of XLF.
abstract: Ku heterodimer is essential for the repair of DNA double-strand breaks (DSBs) by non-homologous end-joining (NHEJ). Ku recruits XLF, also known as Cernunnos, to DSBs. Here we report domain analyses of Ku-XLF interaction. The heterodimeric domain of Ku was found to be sufficient for the recruitment of XLF to DSBs and for the interaction of Ku with XLF. A small C-terminal deletion of XLF completely abolished recruitment of XLF to DSBs and Ku-XLF interaction. This deletion also led to marked reduction of XLF-XRCC4 interaction although the XRCC4-binding site on the XLF N-terminal domain remained intact. These results demonstrate the significance of Ku-XLF interaction in the molecular assembly of NHEJ factors.
authors.affiliation: Bioelectrics Research Center, Kumamoto University, 2-39-1 Kurokami, Kumamoto 860-8555, Japan. yanoken@kumamoto-u.ac.jp
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Yano
authors.forename: Keiko
authors.initials: K
authors.lastname: Morotomi-Yano
authors.forename: Kyung-Jong
authors.initials: KJ
authors.lastname: Lee
authors.forename: David J
authors.initials: DJ
authors.lastname: Chen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D034961:Antigens, Nuclear / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D000072200:Ku Autoantigen; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D055503:Protein Multimerization
chemical_list: D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D008164:Luminescent Proteins; C508551:NHEJ1 protein, human; C101467:XRCC4 protein, human; C000606509:Xrcc6 protein, human; C000606510:Xrcc6 protein, mouse; D000072200:Ku Autoantigen; D045643:DNA Repair Enzymes