title: Chromosome-wide Rad51 spreading and SUMO-H2A.Z-dependent chromosome fixation in response to a persistent DNA double-strand break.
abstract: DNA double-strand breaks (DSBs) are acutely hazardous for cells, as they can cause genome instability. DSB repair involves the sequential recruitment of repair factors to the DSBs, followed by Rad51-mediated homology probing, DNA synthesis, and ligation. However, little is known about how cells react if no homology is found and DSBs persist. Here, by monitoring a single persistent DNA break, we show that, following DNA resection and RPA recruitment, Rad51 spreads chromosome-wide bidirectionally from the DSB but selectively only on the broken chromosome. Remarkably, the persistent DSB is later fixed to the nuclear periphery in a process that requires Rad51, the histone variant H2A.Z, its SUMO modification, and the DNA-damage checkpoint. Indeed, H2A.Z is deposited close to the break early but transiently and directs DNA resection, single DSB-induced checkpoint activation, and DSB anchoring. Thus, a persistent DSB induces a multifaceted response, which is linked to a specific chromatin mark.
authors.affiliation: Department of Molecular Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
authors.forename: Marian
authors.initials: M
authors.lastname: Kalocsay
authors.forename: Natalie Jasmin
authors.initials: NJ
authors.lastname: Hiller
authors.forename: Stefan
authors.initials: S
authors.lastname: Jentsch
mesh_terms: D015825:Chromosomes, Fungal / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded; D004271:DNA, Fungal / Q000032:analysis / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D009685:Nuclear Envelope / Q000378:metabolism; D051135:Rad51 Recombinase / Q000378:metabolism*; D025842:SUMO-1 Protein / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D004271:DNA, Fungal; D006657:Histones; D025842:SUMO-1 Protein; D029701:Saccharomyces cerevisiae Proteins; C495151:RAD51 protein, S cerevisiae; D051135:Rad51 Recombinase