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Myc-Dependent Genome Instability and Lifespan in Drosophila

Authors: Greer, Christina; Lee, Moonsook; Westerhof, Maaike; Milholland, Brandon; Spokony, Rebecca; Vijg, Jan; Secombe, Julie;

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.

Country
United States
Related Organizations
Keywords

570, Aging, DNA Repair, Science, DNA Mutational Analysis, Green Fluorescent Proteins, 590, Genomic Instability, Histones, Animals, Drosophila Proteins, DNA Breaks, Double-Stranded, Transgenes, Gene Rearrangement, Genome, Q, R, DNA-Binding Proteins, Lac Operon, Mutation, Medicine, Drosophila, Research Article, Transcription Factors

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    selected citations
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    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
46
Top 10%
Top 10%
Top 10%
Green
gold
Related to Research communities
Cancer Research