Requirement of ATR for maintenance of intestinal stem cells in aging Drosophila.
Aging (Albany NY)
; 7(5): 307-18, 2015 May.
Article
em En
| MEDLINE
| ID: mdl-26000719
ABSTRACT
The stem cell genomic stability forms the basis for robust tissue homeostasis, particularly in high-turnover tissues. For the genomic stability, DNA damage response (DDR) is essential. This study was focused on the role of two major DDR-related factors, ataxia telangiectasia-mutated (ATM) and ATM- and RAD3-related (ATR) kinases, in the maintenance of intestinal stem cells (ISCs) in the adultDrosophila midgut. We explored the role of ATM and ATR, utilizing immunostaining with an anti-pS/TQ antibody as an indicator of ATM/ATR activation, γ-irradiation as a DNA damage inducer, and the UAS/GAL4 system for cell type-specific knockdown of ATM, ATR, or both during adulthood. The results showed that the pS/TQ signals got stronger with age and after oxidative stress. The pS/TQ signals were found to be more dependent on ATR rather than on ATM in ISCs/enteroblasts (EBs). Furthermore, an ISC/EB-specific knockdown of ATR, ATM, or both decreased the number of ISCs and oxidative stress-induced ISC proliferation. The phenotypic changes that were caused by the ATR knockdown were more pronounced than those caused by the ATM knockdown; however, our data indicate that ATR and ATM are both needed for ISC maintenance and proliferation; ATR seems to play a bigger role than does ATM.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Células-Tronco
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Proteínas Serina-Treonina Quinases
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Proteínas de Ciclo Celular
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Proteínas de Drosophila
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Células-Tronco Adultas
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Proteínas Mutadas de Ataxia Telangiectasia
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Intestinos
Limite:
Animals
Idioma:
En
Revista:
Aging (Albany NY)
Assunto da revista:
GERIATRIA
Ano de publicação:
2015
Tipo de documento:
Article