Retrotransposon overdose and genome integrity

Lisa Z. Scheifele, Gregory J. Cost, Margaret L. Zupancic, Emerita M. Caputo, Jef D. Boeke

    Research output: Contribution to journalArticle

    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.

    Original languageEnglish (US)
    Pages (from-to)13927-13932
    Number of pages6
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume106
    Issue number33
    DOIs
    StatePublished - Aug 18 2009

    Keywords

    • Chromosome rearrangement
    • Genome instability
    • Ty1 elements

    ASJC Scopus subject areas

    • General

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  • Cite this

    Scheifele, L. Z., Cost, G. J., Zupancic, M. L., Caputo, E. M., & Boeke, J. D. (2009). Retrotransposon overdose and genome integrity. Proceedings of the National Academy of Sciences of the United States of America, 106(33), 13927-13932. https://doi.org/10.1073/pnas.0906552106