title: PolySUMOylation by Siz2 and Mms21 triggers relocation of DNA breaks to nuclear pores through the Slx5/Slx8 STUbL.
abstract: High-resolution imaging shows that persistent DNA damage in budding yeast localizes in distinct perinuclear foci for repair. The signals that trigger DNA double-strand break (DSB) relocation or determine their destination are unknown. We show here that DSB relocation to the nuclear envelope depends on SUMOylation mediated by the E3 ligases Siz2 and Mms21. In G1, a polySUMOylation signal deposited coordinately by Mms21 and Siz2 recruits the SUMO targeted ubiquitin ligase Slx5/Slx8 to persistent breaks. Both Slx5 and Slx8 are necessary for damage relocation to nuclear pores. When targeted to an undamaged locus, however, Slx5 alone can mediate relocation in G1-phase cells, bypassing the requirement for polySUMOylation. In contrast, in S-phase cells, monoSUMOylation mediated by the Rtt107-stabilized SMC5/6-Mms21 E3 complex drives DSBs to the SUN domain protein Mps3 in a manner independent of Slx5. Slx5/Slx8 and binding to pores favor repair by ectopic break-induced replication and imprecise end-joining.
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, CH-4058 Basel, Switzerland;
authors.forename: Chihiro
authors.initials: C
authors.lastname: Horigome
authors.affiliation: Department of Biochemistry and Molecular Biology, Robson DNA Science Centre, Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta T2N 4N1, Canada; Department of Oncology, Robson DNA Science Centre, Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta T2N 4N1, Canada;
authors.forename: Denise E
authors.initials: DE
authors.lastname: Bustard
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, CH-4058 Basel, Switzerland; Faculty of Natural Sciences, University of Basel, CH-4056 Basel, Switzerland.
authors.forename: Isabella
authors.initials: I
authors.lastname: Marcomini
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, CH-4058 Basel, Switzerland;
authors.forename: Neda
authors.initials: N
authors.lastname: Delgoshaie
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, CH-4058 Basel, Switzerland;
authors.forename: Monika
authors.initials: M
authors.lastname: Tsai-Pflugfelder
authors.affiliation: Department of Biochemistry and Molecular Biology, Robson DNA Science Centre, Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta T2N 4N1, Canada; Department of Oncology, Robson DNA Science Centre, Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta T2N 4N1, Canada;
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Cobb
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, CH-4058 Basel, Switzerland; Faculty of Natural Sciences, University of Basel, CH-4056 Basel, Switzerland.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Gasser
mesh_terms: D053903:DNA Breaks, Double-Stranded; D009154:Mutation; D009685:Nuclear Envelope / Q000378:metabolism; D022022:Nuclear Pore / Q000378:metabolism*; D011485:Protein Binding; D016196:S Phase / Q000502:physiology; D025842:SUMO-1 Protein / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D058207:Sumoylation; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: C500948:Mms21 protein, S cerevisiae; D025842:SUMO-1 Protein; D029701:Saccharomyces cerevisiae Proteins; C436836:Siz2 protein, S cerevisiae; C515574:Slx8 protein, S cerevisiae; D044767:Ubiquitin-Protein Ligases; C515573:Slx5 protein, S cerevisiae
keywords: DNA damage; Mms21; SUMO; Siz2; Slx5; nuclear organization; nuclear pores