Shelterin and subtelomeric DNA sequences control nucleosome maintenance and genome stability. (12th November 2018)

• Record Type: Journal Article
• Authors: van Emden, Thomas S; Forn, Marta; Forné, Ignasi; Sarkadi, Zsuzsa; Capella, Matías; Martín Caballero, Lucía; Fischer‐Burkart, Sabine; Brönner, Cornelia; Simonetta, Marco; Toczyski, David; Halic, Mario; Imhof, Axel; Braun, Sigurd
• Is Part Of: EMBO reports. Volume 20:Number 1(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-11-12
• Subjects: genome stability -- heterochromatin -- nucleosomes -- shelterin -- telomeres; Molecular biology -- Periodicals; Molecular Biology -- Periodicals; Molecular biology; Periodicals; 572.8
• DOI: 10.15252/embr.201847181
• Languages: English
• ISSNs: 1469-221X

Abstract

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. Synopsis: The AT‐rich telomere‐associated sequences (TAS) in S. pombe are hyper‐recombinogenic and have metastable nucleosomes. This fragile nature of subtelomeres is counteracted by the shelterin subunit Ccq1 and its downstream partners CLRC and SHREC. Ccq1 protects TAS from nucleosome loss by recruiting the heterochromatic repressor complexes CLRC and SHREC. Nucleosome instability is independent of the chromosomal position and an intrinsic feature of the subtelomeric DNA sequence. TAS promote recombination of chromosomal ends in the absence of Ccq1. Abstract : The AT‐rich telomere‐associated sequences (TAS) in S. pombe are hyper‐recombinogenic and have metastable nucleosomes. This fragile nature of subtelomeres is counteracted by the shelterin subunit Ccq1 and its downstream partners CLRC and SHREC.