title: Expansion of Interstitial Telomeric Sequences in Yeast.
abstract: Telomeric repeats located within chromosomes are called interstitial telomeric sequences (ITSs). They are polymorphic in length and are likely hotspots for initiation of chromosomal rearrangements that have been linked to human disease. Using our S. cerevisiae system to study repeat-mediated genome instability, we have previously shown that yeast telomeric (Ytel) repeats induce various gross chromosomal rearrangements (GCR) when their G-rich strands serve as the lagging strand template for replication (G orientation). Here, we show that interstitial Ytel repeats in the opposite C orientation prefer to expand rather than cause GCR. A tract of eight Ytel repeats expands at a rate of 4 × 10(-4) per replication, ranking them among the most expansion-prone DNA microsatellites. A candidate-based genetic analysis implicates both post-replication repair and homologous recombination pathways in the expansion process. We propose a model for Ytel repeat expansions and discuss its applications for genome instability and alternative telomere lengthening (ALT).
authors.affiliation: Department of Biology, Tufts University, Medford, MA 02155, USA; Department of Genetics, St. Petersburg State University, St. Petersburg 199034, Russia.
authors.forename: Anna Y
authors.initials: AY
authors.lastname: Aksenova
authors.affiliation: Department of Biology, Tufts University, Medford, MA 02155, USA.
authors.forename: Gil
authors.initials: G
authors.lastname: Han
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Shishkin
authors.affiliation: Department of Genetics, St. Petersburg State University, St. Petersburg 199034, Russia.
authors.forename: Kirill V
authors.initials: KV
authors.lastname: Volkov
authors.affiliation: Department of Biology, Tufts University, Medford, MA 02155, USA. Electronic address: sergei.mirkin@tufts.edu.
authors.forename: Sergei M
authors.initials: SM
authors.lastname: Mirkin
mesh_terms: D002869:Chromosome Aberrations; D004260:DNA Repair / Q000235:genetics; D004261:DNA Replication / Q000235:genetics; D004271:DNA, Fungal / Q000235:genetics; D042822:Genomic Instability / Q000235:genetics; D059765:Homologous Recombination / Q000235:genetics; D018895:Microsatellite Repeats / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D016615:Telomere / Q000235:genetics*
chemical_list: D004271:DNA, Fungal