TASks for subtelomeres: when nucleosome loss and genome instability are favored
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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.
KeywordsSubtelomeres Shelterin Nucleosomes Genome stability Heterochromatin
We thank the members of the Braun Lab for critical reading of this manuscript. This work was supported by grants awarded to S.B. from the German Research Foundation (BR 3511/2-1; SFB 1064-A25) and the European Union Network of Excellence EpiGeneSys (HEALTH-2010-257082).
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Conflict of interest
The authors declare that they have no conflict of interest.
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