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.
|
Authors | Joung-Sun Park, Hyun-Jin Na, Jung-Hoon Pyo, Ho-Jun Jeon, Young-Shin Kim, Mi-Ae Yoo |
Journal | Aging
(Aging (Albany NY))
Vol. 7
Issue 5
Pg. 307-18
(May 2015)
ISSN: 1945-4589 [Electronic] United States |
PMID | 26000719
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Cell Cycle Proteins
- Drosophila Proteins
- Ataxia Telangiectasia Mutated Proteins
- Mei-41 protein, Drosophila
- Protein Serine-Threonine Kinases
- Tefu protein, Drosophila
|
Topics |
- Adult Stem Cells
(cytology, metabolism)
- Aging
- Animals
- Ataxia Telangiectasia Mutated Proteins
(metabolism)
- Cell Cycle Proteins
(metabolism)
- Drosophila
- Drosophila Proteins
(metabolism)
- Immunohistochemistry
- Intestines
(cytology)
- Protein Serine-Threonine Kinases
(metabolism)
- Stem Cells
(cytology, metabolism)
|