title: SWR1 and INO80 chromatin remodelers contribute to DNA double-strand break perinuclear anchorage site choice.
abstract: Persistent DNA double-strand breaks (DSBs) are recruited to the nuclear periphery in budding yeast. Both the Nup84 pore subcomplex and Mps3, an inner nuclear membrane (INM) SUN domain protein, have been implicated in DSB binding. It was unclear what, if anything, distinguishes the two potential sites of repair. Here, we characterize and distinguish the two binding sites. First, DSB-pore interaction occurs independently of cell-cycle phase and requires neither the chromatin remodeler INO80 nor recombinase Rad51 activity. In contrast, Mps3 binding is S and G2 phase specific and requires both factors. SWR1-dependent incorporation of Htz1 (H2A.Z) is necessary for break relocation to either site in both G1- and S-phase cells. Importantly, functional assays indicate that mutations in the two sites have additive repair defects, arguing that the two perinuclear anchorage sites define distinct survival pathways.
authors: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
authors: Chihiro
authors: C
authors: Horigome
authors: Laboratory of Molecular Biology, Tohoku University, Tsutsumidori-Amamiyamachi 1-1, Aoba-ku, Sendai 981-8555, Japan.
authors: Yukako
authors: Y
authors: Oma
authors: Laboratory of Molecular Biology, Tohoku University, Tsutsumidori-Amamiyamachi 1-1, Aoba-ku, Sendai 981-8555, Japan.
authors: Tatsunori
authors: T
authors: Konishi
authors: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland; Institute of Plant Biology, University of Zurich, Zollikerstrasse 107, 8008 Zurich, Switzerland.
authors: Roger
authors: R
authors: Schmid
authors: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland; University of Basel, Faculty of Natural Sciences, 4056 Basel, Switzerland.
authors: Isabella
authors: I
authors: Marcomini
authors: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland; University of Basel, Faculty of Natural Sciences, 4056 Basel, Switzerland.
authors: Michael H
authors: MH
authors: Hauer
authors: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
authors: Vincent
authors: V
authors: Dion
authors: Laboratory of Molecular Biology, Tohoku University, Tsutsumidori-Amamiyamachi 1-1, Aoba-ku, Sendai 981-8555, Japan.
authors: Masahiko
authors: M
authors: Harata
authors: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland; University of Basel, Faculty of Natural Sciences, 4056 Basel, Switzerland. Electronic address: susan.gasser@fmi.ch.
authors: Susan M
authors: SM
authors: Gasser
mesh_terms: D000251:Adenosine Triphosphatases / Q000502:physiology; D001665:Binding Sites / Q000235:genetics* / Q000502:physiology; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D042002:Chromatin Assembly and Disassembly / Q000235:genetics / Q000502:physiology*; D053903:DNA Breaks, Double-Stranded; D004271:DNA, Fungal / Q000235:genetics*; D005656:Fungal Proteins / Q000502:physiology*; D006657:Histones / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D009154:Mutation; D004718:Saccharomycetales / Q000235:genetics* / Q000378:metabolism
chemical_list: D004271:DNA, Fungal; D005656:Fungal Proteins; D006657:Histones; D008565:Membrane Proteins; D000251:Adenosine Triphosphatases