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DNA Synthesis Generates Terminal Duplications That Seal End-to-End Chromosome Fusions

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Science  22 Apr 2011:
Vol. 332, Issue 6028, pp. 468-471
DOI: 10.1126/science.1199022

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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.

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