Ontogeny of Unstable Chromosomes Generated by Telomere Error in Budding Yeast

Tracey Beyer, Ted Weinert

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

DNA 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.

Original languageEnglish (US)
Article numbere1006345
JournalPLoS Genetics
Volume12
Issue number10
DOIs
StatePublished - Oct 1 2016

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Saccharomycetales
telomeres
Telomere
ontogeny
yeast
chromosome
Chromosomes
yeasts
chromosomes
Isochromosomes
Genome
genomics
DNA Helicases
genome
Chromosomal Instability
DNA helicases
Telomerase
Genetic Models
DNA
telomerase

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

Cite this

Ontogeny of Unstable Chromosomes Generated by Telomere Error in Budding Yeast. / Beyer, Tracey; Weinert, Ted.

In: PLoS Genetics, Vol. 12, No. 10, e1006345, 01.10.2016.

Research output: Contribution to journalArticle

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