title: SUMO-Dependent Relocalization of Eroded Telomeres to Nuclear Pore Complexes Controls Telomere Recombination.
abstract: In budding yeast, inactivation of telomerase and ensuing telomere erosion cause relocalization of telomeres to nuclear pore complexes (NPCs). However, neither the mechanism of such relocalization nor its significance are understood. We report that proteins bound to eroded telomeres are recognized by the SUMO (small ubiquitin-like modifier)-targeted ubiquitin ligase (STUbL) Slx5-Slx8 and become increasingly SUMOylated. Recruitment of Slx5-Slx8 to eroded telomeres facilitates telomere relocalization to NPCs and type II telomere recombination, a counterpart of mammalian alternative lengthening of telomeres (ALT). Moreover, artificial tethering of a telomere to a NPC promotes type II telomere recombination but cannot bypass the lack of Slx5-Slx8 in this process. Together, our results indicate that SUMOylation positively contributes to telomere relocalization to the NPC, where poly-SUMOylated proteins that accumulated over time have to be removed. We propose that STUbL-dependent relocalization of telomeres to NPCs constitutes a pathway in which excessively SUMOylated proteins are removed from "congested" intermediates to ensure unconventional recombination.
authors.affiliation: Marseille Cancer Research Center (CRCM), U1068 INSERM, UMR7258 CNRS, Aix Marseille University, Institut Paoli-Calmettes (Equipe labellisée Ligue), Marseille 13009, France.
authors.forename: Dmitri
authors.initials: D
authors.lastname: Churikov
authors.affiliation: Marseille Cancer Research Center (CRCM), U1068 INSERM, UMR7258 CNRS, Aix Marseille University, Institut Paoli-Calmettes (Equipe labellisée Ligue), Marseille 13009, France.
authors.forename: Ferose
authors.initials: F
authors.lastname: Charifi
authors.affiliation: Department of Biology, University of Copenhagen, 2200 Copenhagen N, Denmark.
authors.forename: Nadine
authors.initials: N
authors.lastname: Eckert-Boulet
authors.affiliation: Department of Biology, University of Copenhagen, 2200 Copenhagen N, Denmark.
authors.forename: Sonia
authors.initials: S
authors.lastname: Silva
authors.affiliation: Marseille Cancer Research Center (CRCM), U1068 INSERM, UMR7258 CNRS, Aix Marseille University, Institut Paoli-Calmettes (Equipe labellisée Ligue), Marseille 13009, France. Electronic address: marie-noelle.simon@inserm.fr.
authors.forename: Marie-Noelle
authors.initials: MN
authors.lastname: Simon
authors.affiliation: Department of Biology, University of Copenhagen, 2200 Copenhagen N, Denmark. Electronic address: mlisby@bio.ku.dk.
authors.forename: Michael
authors.initials: M
authors.lastname: Lisby
authors.affiliation: Marseille Cancer Research Center (CRCM), U1068 INSERM, UMR7258 CNRS, Aix Marseille University, Institut Paoli-Calmettes (Equipe labellisée Ligue), Marseille 13009, France. Electronic address: vincent.geli@inserm.fr.
authors.forename: Vincent
authors.initials: V
authors.lastname: Géli
mesh_terms: D022022:Nuclear Pore / Q000378:metabolism*; D011485:Protein Binding; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D058207:Sumoylation; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; D044767:Ubiquitin-Protein Ligases; D019098:Telomerase