Inner nuclear membrane protein Lem2 augments heterochromatin formation in response to nutritional conditions

Genes Cells. 2016 Aug;21(8):812-32. doi: 10.1111/gtc.12385. Epub 2016 Jun 23.


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.

MeSH terms

  • Chromatin Assembly and Disassembly / genetics*
  • Endoplasmic Reticulum / genetics
  • Heterochromatin / genetics*
  • Lamin Type A / genetics
  • Mutation
  • Nuclear Envelope / genetics
  • Nuclear Proteins / genetics
  • Schizosaccharomyces / genetics*
  • Schizosaccharomyces pombe Proteins / genetics*
  • Telomere / genetics


  • Heterochromatin
  • Lamin Type A
  • Nuclear Proteins
  • Schizosaccharomyces pombe Proteins