title: Inner nuclear membrane protein Lem2 augments heterochromatin formation in response to nutritional conditions.
abstract: Inner nuclear membrane proteins interact with chromosomes in the nucleus and are important for chromosome activity. Lem2 and Man1 are conserved members of the LEM-domain nuclear membrane protein family. Mutations of LEM-domain proteins are associated with laminopathy, but their cellular functions remain unclear. Here, we report that Lem2 maintains genome stability in the fission yeast Schizosaccharomyces pombe. S. pombe cells disrupted for the lem2(+) gene (lem2∆) showed slow growth and increased rate of the minichromosome loss. These phenotypes were prominent in the rich culture medium, but not in the minimum medium. Centromeric heterochromatin formation was augmented upon transfer to the rich medium in wild-type cells. This augmentation of heterochromatin formation was impaired in lem2∆ cells. Notably, lem2∆ cells occasionally exhibited spontaneous duplication of genome sequences flanked by the long-terminal repeats of retrotransposons. The resulting duplication of the lnp1(+) gene, which encodes an endoplasmic reticulum membrane protein, suppressed lem2∆ phenotypes, whereas the lem2∆ lnp1∆ double mutant showed a severe growth defect. A combination of mutations in Lem2 and Bqt4, which encodes a nuclear membrane protein that anchors telomeres to the nuclear membrane, caused synthetic lethality. These genetic interactions imply that Lem2 cooperates with the nuclear membrane protein network to regulate genome stability.
authors.affiliation: Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka, Suita, 565-0871, Japan.|Advanced ICT Research Institute Kobe, National Institute of Information and Communications Technology, 588-2 Iwaoka, Iwaoka-cho, Nishi-ku, Kobe, 651-2492, Japan.
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Tange
authors.affiliation: Advanced ICT Research Institute Kobe, National Institute of Information and Communications Technology, 588-2 Iwaoka, Iwaoka-cho, Nishi-ku, Kobe, 651-2492, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Chikashige
authors.affiliation: Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo, 060-0810, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Takahata
authors.affiliation: Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo, 060-0810, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Kawakami
authors.affiliation: Graduate school of Chemical Sciences and Engineering, Hokkaido University, Sapporo, 060-0810, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Higashi
authors.affiliation: Advanced ICT Research Institute Kobe, National Institute of Information and Communications Technology, 588-2 Iwaoka, Iwaoka-cho, Nishi-ku, Kobe, 651-2492, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Mori
authors.affiliation: Advanced ICT Research Institute Kobe, National Institute of Information and Communications Technology, 588-2 Iwaoka, Iwaoka-cho, Nishi-ku, Kobe, 651-2492, Japan.|Laboratory of Electron Microscopy, Faculty of Science, Japan Women's University, 2-8-1 Mejirodai, Bunkyo-ku, Tokyo, 112-8681, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kojidani
authors.affiliation: Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka, Suita, 565-0871, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Hirano
authors.affiliation: Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka, Suita, 565-0871, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Asakawa
authors.affiliation: Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo, 060-0810, Japan.
authors.forename: Yota
authors.initials: Y
authors.lastname: Murakami
authors.affiliation: Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka, Suita, 565-0871, Japan.|Advanced ICT Research Institute Kobe, National Institute of Information and Communications Technology, 588-2 Iwaoka, Iwaoka-cho, Nishi-ku, Kobe, 651-2492, Japan.
authors.forename: Tokuko
authors.initials: T
authors.lastname: Haraguchi
authors.affiliation: Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka, Suita, 565-0871, Japan.|Advanced ICT Research Institute Kobe, National Institute of Information and Communications Technology, 588-2 Iwaoka, Iwaoka-cho, Nishi-ku, Kobe, 651-2492, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hiraoka
mesh_terms: D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D004721:Endoplasmic Reticulum / Q000235:genetics; D006570:Heterochromatin / Q000235:genetics*; D034904:Lamin Type A / Q000235:genetics; D009154:Mutation; D009685:Nuclear Envelope / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D012568:Schizosaccharomyces / Q000235:genetics*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics*; D016615:Telomere / Q000235:genetics
chemical_list: D006570:Heterochromatin; D034904:Lamin Type A; D009687:Nuclear Proteins; D029702:Schizosaccharomyces pombe Proteins