Cargando…
Myc-Dependent Genome Instability and Lifespan in Drosophila
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...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3765364/ https://www.ncbi.nlm.nih.gov/pubmed/24040302 http://dx.doi.org/10.1371/journal.pone.0074641 |
_version_ | 1782283291946123264 |
---|---|
author | Greer, Christina Lee, Moonsook Westerhof, Maaike Milholland, Brandon Spokony, Rebecca Vijg, Jan Secombe, Julie |
author_facet | Greer, Christina Lee, Moonsook Westerhof, Maaike Milholland, Brandon Spokony, Rebecca Vijg, Jan Secombe, Julie |
author_sort | Greer, Christina |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3765364 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-37653642013-09-13 Myc-Dependent Genome Instability and Lifespan in Drosophila Greer, Christina Lee, Moonsook Westerhof, Maaike Milholland, Brandon Spokony, Rebecca Vijg, Jan Secombe, Julie PLoS One Research Article 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. Public Library of Science 2013-09-06 /pmc/articles/PMC3765364/ /pubmed/24040302 http://dx.doi.org/10.1371/journal.pone.0074641 Text en © 2013 Greer et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Greer, Christina Lee, Moonsook Westerhof, Maaike Milholland, Brandon Spokony, Rebecca Vijg, Jan Secombe, Julie Myc-Dependent Genome Instability and Lifespan in Drosophila |
title | Myc-Dependent Genome Instability and Lifespan in Drosophila
|
title_full | Myc-Dependent Genome Instability and Lifespan in Drosophila
|
title_fullStr | Myc-Dependent Genome Instability and Lifespan in Drosophila
|
title_full_unstemmed | Myc-Dependent Genome Instability and Lifespan in Drosophila
|
title_short | Myc-Dependent Genome Instability and Lifespan in Drosophila
|
title_sort | myc-dependent genome instability and lifespan in drosophila |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3765364/ https://www.ncbi.nlm.nih.gov/pubmed/24040302 http://dx.doi.org/10.1371/journal.pone.0074641 |
work_keys_str_mv | AT greerchristina mycdependentgenomeinstabilityandlifespanindrosophila AT leemoonsook mycdependentgenomeinstabilityandlifespanindrosophila AT westerhofmaaike mycdependentgenomeinstabilityandlifespanindrosophila AT milhollandbrandon mycdependentgenomeinstabilityandlifespanindrosophila AT spokonyrebecca mycdependentgenomeinstabilityandlifespanindrosophila AT vijgjan mycdependentgenomeinstabilityandlifespanindrosophila AT secombejulie mycdependentgenomeinstabilityandlifespanindrosophila |