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EMBO Rep. 2018 Nov 12. pii: e47181. doi: 10.15252/embr.201847181. [Epub ahead of print]

Shelterin and subtelomeric DNA sequences control nucleosome maintenance and genome stability.

Author information

1
Department of Physiological Chemistry, BioMedical Center (BMC), Ludwig Maximilians University of Munich, Martinsried, Germany.
2
International Max Planck Research School for Molecular and Cellular Life Sciences, Martinsried, Germany.
3
Protein Analysis Unit (ZfP), BioMedical Center (BMC), Ludwig Maximilians University of Munich, Martinsried, Germany.
4
Department of Biochemistry, Gene Center, Ludwig Maximilians University of Munich, Munich, Germany.
5
Department of Biophysics and Biochemistry, University of California San Francisco (UCSF), San Francisco, CA, USA.
6
Department of Physiological Chemistry, BioMedical Center (BMC), Ludwig Maximilians University of Munich, Martinsried, Germany sigurd.braun@bmc.med.lmu.de.

Abstract

Telomeres and the shelterin complex cap and protect the ends of chromosomes. Telomeres are flanked by the subtelomeric sequences that have also been implicated in telomere regulation, although their role is not well defined. Here, we show that, in Schizosaccharomyces pombe, the telomere-associated sequences (TAS) present on most subtelomeres are hyper-recombinogenic, have metastable nucleosomes, and unusual low levels of H3K9 methylation. Ccq1, a subunit of shelterin, protects TAS from nucleosome loss by recruiting the heterochromatic repressor complexes CLRC and SHREC, thereby linking nucleosome stability to gene silencing. Nucleosome instability at TAS is independent of telomeric repeats and can be transmitted to an intrachromosomal locus containing an ectopic TAS fragment, indicating that this is an intrinsic property of the underlying DNA sequence. When telomerase recruitment is compromised in cells lacking Ccq1, DNA sequences present in the TAS promote recombination between chromosomal ends, independent of nucleosome abundance, implying an active function of these sequences in telomere maintenance. We propose that Ccq1 and fragile subtelomeres co-evolved to regulate telomere plasticity by controlling nucleosome occupancy and genome stability.

KEYWORDS:

genome stability; heterochromatin; nucleosomes; shelterin; telomeres

PMID:
30420521
DOI:
10.15252/embr.201847181

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