title: Interaction between RNF8 and DYRK2 is required for the recruitment of DNA repair molecules to DNA double-strand breaks.
abstract: The genome of eukaryotic cells is frequently exposed to damage by various genotoxins. Phosphorylation of histone H2AX at Serine 139 (γ-H2AX) is a hallmark of DNA damage. RNF8 monoubiquitinates γ-H2AX with the Lys63-linked ubiquitin chain to tether DNA repair molecules at DNA lesions. A high-throughput screening identified RNF8 as a binding partner of dual-specificity tyrosine phosphorylation-regulated kinase 2 (DYRK2). Notably, DNA damage-induced monoubiquitination of γ-H2AX is impaired in DYRK2-depleted cells. The foci formation of p53-binding protein 1 at DNA double-strand break sites is suppressed in DYRK2 knockdown cells, which fail to repair the DNA damage. A homologous recombination assay showed decreased repair efficiency in DYRK2-depleted cells. Our findings indicate direct interaction of DYRK2 with RNF8 in regulating response to DNA damage.
authors.affiliation: Department of Biochemistry, Jikei University School of Medicine, Minato-ku, Tokyo, Japan.
authors.forename: Takenori
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Department of Biochemistry, Jikei University School of Medicine, Minato-ku, Tokyo, Japan.
authors.forename: Naoe
authors.initials: N
authors.lastname: Taira Nihira
authors.affiliation: Department of Biochemistry, Jikei University School of Medicine, Minato-ku, Tokyo, Japan.
authors.forename: Satomi
authors.initials: S
authors.lastname: Yogosawa
authors.affiliation: Department of Biochemistry, Jikei University School of Medicine, Minato-ku, Tokyo, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Aoki
authors.affiliation: Cell-Free Science and Technology Research Center, Ehime University, Matsuyama, Ehime, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takeda
authors.affiliation: Cell-Free Science and Technology Research Center, Ehime University, Matsuyama, Ehime, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Sawasaki
authors.affiliation: Department of Biochemistry, Jikei University School of Medicine, Minato-ku, Tokyo, Japan.
authors.forename: Kiyotsugu
authors.initials: K
authors.lastname: Yoshida
mesh_terms: D045744:Cell Line, Tumor; D004247:DNA / Q000235:genetics / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D018613:Microscopy, Confocal; D009154:Mutation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination; D000097603:Dyrk Kinases
chemical_list: D004247:DNA; D004268:DNA-Binding Proteins; D006657:Histones; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D051736:Proto-Oncogene Proteins c-mdm2; D016159:Tumor Suppressor Protein p53; D044767:Ubiquitin-Protein Ligases; D000097603:Dyrk Kinases; C468783:H2AX protein, human; C486521:RNF8 protein, human; C497206:MDM2 protein, human
keywords: DNA damage; DNA repair; DYRK2; RNF8; γH2AX monoubiquitination