title: Acentric chromosome ends are prone to fusion with functional chromosome ends through a homology-directed rearrangement.
abstract: The centromeres of many eukaryotic chromosomes are established epigenetically on potentially variable tandem repeats; hence, these chromosomes are at risk of being acentric. We reported previously that artificially created acentric chromosomes in the fission yeast Schizosaccharomyces pombe can be rescued by end-to-end fusion with functional chromosomes. Here, we show that most acentric/functional chromosome fusion events in S. pombe cells harbouring an acentric chromosome I differed from the non-homologous end-joining-mediated rearrangements that result in deleterious dicentric fusions in normal cells, and were elicited by a previously unidentified homologous recombination (HR) event between chromosome end-associated sequences. The subtelomere repeats associated with the non-fusogenic ends were also destabilized in the surviving cells, suggesting a causal link between general subtelomere destabilization and acentric/functional chromosome fusion. A mutational analysis indicated that a non-canonical HR pathway was involved in the rearrangement. These findings are indicative of a latent mechanism that conditionally induces general subtelomere instability, presumably in the face of accidental centromere loss events, resulting in rescue of the fatal acentric chromosomes by interchromosomal HR.
authors.affiliation: Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ohno
authors.affiliation: Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ogiyama
authors.affiliation: Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Yoshino
authors.initials: Y
authors.lastname: Kubota
authors.affiliation: Graduate School of Environmental Science, Hokkaido University, Sapporo, Hokkaido 060-0810, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Kubo
authors.affiliation: Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan Institute for Academic Initiatives, Osaka University, Suita, Osaka 565-0871, Japan ishii@fbs.osaka-u.ac.jp.
authors.forename: Kojiro
authors.initials: K
authors.lastname: Ishii
mesh_terms: D002874:Chromosome Mapping; D015825:Chromosomes, Fungal; D053903:DNA Breaks, Double-Stranded; D059766:DNA End-Joining Repair; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D015321:Gene Rearrangement; D042822:Genomic Instability; D059765:Homologous Recombination; D008954:Models, Biological; D051135:Rad51 Recombinase / Q000172:deficiency; D012568:Schizosaccharomyces / Q000235:genetics; D016615:Telomere
chemical_list: D005656:Fungal Proteins; D051135:Rad51 Recombinase