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Myc-dependent genome instability and lifespan in Drosophila.
- Source :
-
PloS one [PLoS One] 2013 Sep 06; Vol. 8 (9), pp. e74641. Date of Electronic Publication: 2013 Sep 06 (Print Publication: 2013). - Publication Year :
- 2013
-
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.
- Subjects :
- Animals
DNA Breaks, Double-Stranded
DNA Mutational Analysis
DNA Repair
DNA-Binding Proteins genetics
Drosophila metabolism
Drosophila Proteins genetics
Gene Rearrangement
Genome
Green Fluorescent Proteins metabolism
Histones chemistry
Lac Operon
Mutation
Transcription Factors genetics
Transgenes
Aging
DNA-Binding Proteins metabolism
Drosophila genetics
Drosophila Proteins metabolism
Genomic Instability
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 8
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 24040302
- Full Text :
- https://doi.org/10.1371/journal.pone.0074641