Cycles of chromosome instability are associated with a fragile site and are increased by defects in DNA replication and checkpoint controls in yeast

Anthony Admire, Lisa Shanks, Nicole Danzl, Mei Wang, Ulli Weier, William Stevens, Elizabeth Hunt, Ted Weinert

Research output: Contribution to journalArticle

99 Scopus citations

Abstract

We report here that a normal budding yeast chromosome (ChrVII) can undergo remarkable cycles of chromosome instability. The events associated with cycles of instability caused a distinctive "sectoring" of colonies on selective agar plates. We found that instability initiated at any of several sites on ChrVII, and was sharply increased by the disruption of DNA replication or by defects in checkpoint controls. We studied in detail the cycles of instability associated with one particular chromosomal site (the "403 site"). This site contained multiple tRNA genes known to stall replication forks, and when deleted, the overall frequency of sectoring was reduced. Instability of the 403 site involved multiple nonallelic recombination events that led to the formation of a monocentric translocation. This translocation remained unstable, frequently undergoing either loss or recombination events linked to the translocation junction. These results suggest a model in which instability initiates at specific chromosomal sites that stall replication forks. Forks not stabilized by checkpoint proteins break and undergo multiple rounds of nonallelic recombination to form translocations. Some translocations remain unstable because they join two "incompatible" chromosomal regions. Cycles of instability of this normal yeast chromosome may be relevant to chromosome instability of mammalian fragile sites and of chromosomes in cancer cells.

Original languageEnglish (US)
Pages (from-to)159-173
Number of pages15
JournalGenes and Development
Volume20
Issue number2
DOIs
StatePublished - Jan 15 2006

Keywords

  • Checkpoints
  • Chromosome instability
  • Fragile sites

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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