title: Myc-dependent genome instability and lifespan in Drosophila.
abstract: The Myc family of transcription factors are key regulators of cell growth and proliferation that are dysregulated in a large number of human cancers. When overexpressed, Myc family proteins also cause genomic instability, a hallmark of both transformed and aging cells. Using an in vivo lacZ mutation reporter, we show that overexpression of Myc in Drosophila increases the frequency of large genome rearrangements associated with erroneous repair of DNA double-strand breaks (DSBs). In addition, we find that overexpression of Myc shortens adult lifespan and, conversely, that Myc haploinsufficiency reduces mutation load and extends lifespan. Our data provide the first evidence that Myc may act as a pro-aging factor, possibly through its ability to greatly increase genome instability.
authors.affiliation: Department of Genetics, Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors.forename: Christina
authors.initials: C
authors.lastname: Greer
authors.forename: Moonsook
authors.initials: M
authors.lastname: Lee
authors.forename: Maaike
authors.initials: M
authors.lastname: Westerhof
authors.forename: Brandon
authors.initials: B
authors.lastname: Milholland
authors.forename: Rebecca
authors.initials: R
authors.lastname: Spokony
authors.forename: Jan
authors.initials: J
authors.lastname: Vijg
authors.forename: Julie
authors.initials: J
authors.lastname: Secombe
mesh_terms: D000375:Aging; D000818:Animals; D053903:DNA Breaks, Double-Stranded; D004252:DNA Mutational Analysis; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D015321:Gene Rearrangement; D016678:Genome; D042822:Genomic Instability; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006657:Histones / Q000737:chemistry; D007763:Lac Operon; D009154:Mutation; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D019076:Transgenes
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D006657:Histones; C102284:Myc protein, Drosophila; D014157:Transcription Factors; D049452:Green Fluorescent Proteins
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