TASks for subtelomeres: when nucleosome loss and genome instability are favored

Curr Genet. 2019 Oct;65(5):1153-1160. doi: 10.1007/s00294-019-00986-8. Epub 2019 May 7.

Abstract

Chromosome ends are protected from erosion and chromosomal fusions through telomeric repeats and the telomere-binding protein complex shelterin. Imperfect repetitive sequences, known as telomere-associated sequences (TAS), flank the telomeres, yet their function is not well understood. In this perspective, we discuss our recent findings demonstrating that the TAS, in Schizosaccharomyces pombe, are organized into a distinct chromatin domain that is marked by low nucleosome levels and is highly recombinogenic (van Emden et al. in EMBO Rep 20:e47181. https://doi.org/10.15252/embr.201847181 , 2019). Low nucleosome abundance at the TAS is independent of the chromosomal position, but is an intrinsic property of the DNA sequence itself. Critical nucleosome levels are maintained through two heterochromatin complexes recruited by the shelterin subunit Ccq1, which together control gene repression and nucleosome stability. Furthermore, Ccq1 inhibits TAS-facilitated recombination between subtelomeres, yet independently of nucleosome stability. In conclusion, the TAS present a unique chromatin environment causing nucleosome loss and genome instability, which are both counteracted by Ccq1 through independent mechanisms. Given the antagonistic behavior, we hypothesize that Ccq1 co-evolved with the appearance of TAS to regulate nucleosome dynamics and recombination-based telomere maintenance in the absence of telomerase.

Keywords: Genome stability; Heterochromatin; Nucleosomes; Shelterin; Subtelomeres.

Publication types

  • Review

MeSH terms

  • Genomic Instability
  • Heterochromatin / genetics
  • Heterochromatin / metabolism
  • Nucleosomes / genetics
  • Nucleosomes / metabolism
  • Recombination, Genetic
  • Repetitive Sequences, Nucleic Acid*
  • Schizosaccharomyces / genetics
  • Schizosaccharomyces / metabolism
  • Telomere / genetics*
  • Telomere / metabolism
  • Telomere-Binding Proteins / genetics
  • Telomere-Binding Proteins / metabolism

Substances

  • Heterochromatin
  • Nucleosomes
  • Telomere-Binding Proteins