title: Retrotransposon overdose and genome integrity.
abstract: Yeast and mammalian genomes are replete with nearly identical copies of long dispersed repeats in the form of retrotransposons. Mechanisms clearly exist to maintain genome structure in the face of potential rearrangement between the dispersed repeats, but the nature of this machinery is poorly understood. Here we describe a series of distinct "retrotransposon overdose" (RO) lineages in which the number of Ty1 elements in the Saccharomyces cerevisiae genome has been increased by as much as 10 fold. Although these RO strains are remarkably normal in growth rate, they demonstrate an intrinsic supersensitivity to DNA-damaging agents. We describe the identification of mutants in the DNA replication pathway that enhance this RO-specific DNA damage supersensitivity by promoting ectopic recombination between Ty1 elements. Abrogation of normal DNA replication leads to rampant genome instability primarily in the form of chromosomal aberrations and confirms the central role of DNA replication accuracy in the stabilization of repetitive DNA.
authors: Department of Molecular Biology and Genetics and High Throughput Biology Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors: Lisa Z
authors: LZ
authors: Scheifele
authors: Gregory J
authors: GJ
authors: Cost
authors: Margaret L
authors: ML
authors: Zupancic
authors: Emerita M
authors: EM
authors: Caputo
authors: Jef D
authors: JD
authors: Boeke
mesh_terms: D015825:Chromosomes, Fungal; D004249:DNA Damage; D004260:DNA Repair; D004261:DNA Replication; D004271:DNA, Fungal / Q000235:genetics; D005656:Fungal Proteins / Q000235:genetics; D015321:Gene Rearrangement; D016678:Genome; D016681:Genome, Fungal; D008957:Models, Genetic; D010957:Plasmids / Q000378:metabolism; D011995:Recombination, Genetic; D018626:Retroelements; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics
chemical_list: D004271:DNA, Fungal; D005656:Fungal Proteins; D018626:Retroelements; D029701:Saccharomyces cerevisiae Proteins