Shelterin and subtelomeric DNA sequences control nucleosome maintenance and genome stability
| Autor: | Ignasi Forné, Cornelia Broenner, Axel Imhof, Lucía Martín Caballero, Mario Halic, Thomas S van Emden, Marta Forn, Zsuzsa Sarkadi, Marco Simonetta, Matías Capella, Sabine Fischer-Burkart, David P. Toczyski, Sigurd Braun |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Telomerase
animal structures Heterochromatin Repressor Locus (genetics) Methylation Biochemistry Genomic Instability 03 medical and health sciences 0302 clinical medicine Schizosaccharomyces Genetics Humans Nucleosome Molecular Biology 030304 developmental biology 0303 health sciences biology Articles Telomere biology.organism_classification Subtelomere Shelterin Nucleosomes Cell biology Schizosaccharomyces pombe Schizosaccharomyces pombe Proteins Genome Fungal 030217 neurology & neurosurgery |
| DOI: | 10.1101/405712 |
| Popis: | 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 telo-mere-associated sequences (TAS) present on most subtelomeres are hyper-recombinogenic, have metastable nucleosomes, and unusual low levels of H3K9 methylation. Ccq1, a subunit of shelter-in, 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 se-quences 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 con-trolling nucleosome occupancy and genome stability. |
| Databáze: | OpenAIRE |
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