title: Aggregative organization enhances the DNA end-joining process that is mediated by DNA-dependent protein kinase.
abstract: The occurrence of DNA double-strand breaks in the nucleus provokes in its structural organization a large-scale alteration whose molecular basis is still mostly unclear. Here, we show that double-strand breaks trigger preferential assembly of nucleoproteins in human cellular fractions and that they mediate the separation of large protein-DNA aggregates from aqueous solution. The interaction among the aggregative nucleoproteins presents a dynamic condition that allows the effective interaction of nucleoproteins with external molecules like free ATP and facilitates intrinsic DNA end-joining activity. This aggregative organization is functionally coacervate-like. The key component is DNA-dependent protein kinase (DNA-PK), which can be characterized as a DNA-specific aggregation factor as well as a nuclear scaffold/matrix-interactive factor. In the context of aggregation, the kinase activity of DNA-PK is essential for efficient DNA end-joining. The massive and functional concentration of nucleoproteins on DNA in vitro may represent a possible status of nuclear dynamics in vivo, which probably includes the DNA-PK-dependent response to multiple double-strand breaks.
authors.affiliation: Research Center for Radiation Safety, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Takahagi
authors.forename: Kouichi
authors.initials: K
authors.lastname: Tatsumi
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002482:Cellulose / Q000737:chemistry; D004247:DNA / Q000737:chemistry*; D004249:DNA Damage; D004260:DNA Repair; D051747:DNA-Activated Protein Kinase / Q000737:chemistry*; D004268:DNA-Binding Proteins / Q000737:chemistry; D006801:Humans; D009687:Nuclear Proteins / Q000737:chemistry; D009698:Nucleoproteins / Q000737:chemistry
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D009698:Nucleoproteins; D000255:Adenosine Triphosphate; D002482:Cellulose; D004247:DNA; D051747:DNA-Activated Protein Kinase