Chromosomal translocations in yeast induced by low levels of DNA polymerase a model for chromosome fragile sites.
In the yeast Saccharomyces cerevisiae, reduced levels of the replicative alpha DNA polymerase result in greatly elevated frequencies of chromosome translocations and chromosome loss. We selected translocations in a small region of chromosome III and found that they involve homologous recombination events between yeast retrotransposons (Ty elements) on chromosome III and retrotransposons located on other chromosomes. One of the two preferred sites of these translocations on chromosome III involve two Ty elements arrayed head-to-head; disruption of this site substantially reduces the rate of translocations. We demonstrate that this pair of Ty elements constitutes a preferred site for double-strand DNA breaks when DNA replication is compromised, analogous to the fragile sites observed in mammalian chromosomes.
Lemoine
Francene J
FJ
Department of Biology and Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Degtyareva
Natasha P
NP
Lobachev
Kirill
K
Petes
Thomas D
TD
D043171:Chromosomal Instability / Q000235:genetics*; D043283:Chromosome Fragile Sites / Q000235:genetics / Q000502:physiology*; D002874:Chromosome Mapping; D004249:DNA Damage / Q000235:genetics; D004256:DNA Polymerase I / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair / Q000235:genetics; D004261:DNA Replication / Q000235:genetics; D015966:Gene Expression Regulation, Fungal / Q000235:genetics; D016681:Genome, Fungal; D020411:Oligonucleotide Array Sequence Analysis; D011995:Recombination, Genetic / Q000235:genetics; D018626:Retroelements / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics*; D014178:Translocation, Genetic / Q000235:genetics*
D018626:Retroelements; D004256:DNA Polymerase I