Ontogeny of Unstable Chromosomes Generated by Telomere Error in Budding Yeast
AffiliationUniv Arizona, Dept Mol & Cellular Biol
MetadataShow full item record
PublisherPUBLIC LIBRARY SCIENCE
CitationOntogeny of Unstable Chromosomes Generated by Telomere Error in Budding Yeast 2016, 12 (10):e1006345 PLOS Genetics
Rights© 2016 Beyer, Weinert. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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AbstractDNA replication errors at certain sites in the genome initiate chromosome instability that ultimately leads to stable genomic rearrangements. Where instability begins is often unclear. And, early instability may form unstable chromosome intermediates whose transient nature also hinders mechanistic understanding. We report here a budding yeast model that reveals the genetic ontogeny of genome rearrangements, from initial replication error to unstable chromosome formation to their resolution. Remarkably, the initial error often arises in or near the telomere, and frequently forms unstable chromosomes. Early unstable chromosomes may then resolve to an internal "collection site" where a dicentric forms and resolves to an isochromosome (other outcomes are possible at each step). The initial telomere-proximal unstable chromosome is increased in mutants in telomerase subunits, Tel1, and even Rad9, with no known telomere-specific function. Defects in Tel1 and in Rrm3, a checkpoint protein kinase with a role in telomere maintenance and a DNA helicase, respectively, synergize dramatically to generate unstable chromosomes, further illustrating the consequence of replication error in the telomere. Collectively, our results suggest telomeric replication errors may be a common cause of seemingly unrelated genomic rearrangements located hundreds of kilobases away.
VersionFinal published version
SponsorsNational Institutes of General Medical Sciences [GM076186-05, GM08659]