title: DNA synthesis generates terminal duplications that seal end-to-end chromosome fusions.
abstract: End-to-end chromosome fusions that occur in the context of telomerase deficiency can trigger genomic duplications. For more than 70 years, these duplications have been attributed solely to breakage-fusion-bridge cycles. To test this hypothesis, we examined end-to-end fusions isolated from Caenorhabditis elegans telomere replication mutants. Genome-level rearrangements revealed fused chromosome ends having interrupted terminal duplications accompanied by template-switching events. These features are very similar to disease-associated duplications of interstitial segments of the human genome. A model termed Fork Stalling and Template Switching has been proposed previously to explain such duplications, where promiscuous replication of large, noncontiguous segments of the genome occurs. Thus, a DNA synthesis-based process may create duplications that seal end-to-end fusions, in the absence of breakage-fusion-bridge cycles.
authors.affiliation: Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Mia Rochelle
authors.initials: MR
authors.lastname: Lowden
authors.forename: Stephane
authors.initials: S
authors.lastname: Flibotte
authors.forename: Donald G
authors.initials: DG
authors.lastname: Moerman
authors.forename: Shawn
authors.initials: S
authors.lastname: Ahmed
mesh_terms: D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism*; D002842:Chromatids / Q000502:physiology; D056905:Chromosome Breakpoints; D058674:Chromosome Duplication; D002875:Chromosomes / Q000502:physiology*; D004261:DNA Replication; D018509:DNA, Helminth / Q000096:biosynthesis*; D055029:Inverted Repeat Sequences; D008957:Models, Genetic; D016133:Polymerase Chain Reaction; D011995:Recombination, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000502:physiology*
chemical_list: D018509:DNA, Helminth; D019098:Telomerase