title: Requirement of ATR for maintenance of intestinal stem cells in aging Drosophila.
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.affiliation: Department of Molecular Biology, Pusan National University, Busan, 609-735, Republic of Korea.
authors.forename: Joung-Sun
authors.initials: JS
authors.lastname: Park
authors.affiliation: Department of Molecular Biology, Pusan National University, Busan, 609-735, Republic of Korea.
authors.forename: Hyun-Jin
authors.initials: HJ
authors.lastname: Na
authors.affiliation: Department of Molecular Biology, Pusan National University, Busan, 609-735, Republic of Korea.
authors.forename: Jung-Hoon
authors.initials: JH
authors.lastname: Pyo
authors.affiliation: Department of Molecular Biology, Pusan National University, Busan, 609-735, Republic of Korea.
authors.forename: Ho-Jun
authors.initials: HJ
authors.lastname: Jeon
authors.affiliation: Department of Molecular Biology, Pusan National University, Busan, 609-735, Republic of Korea.
authors.forename: Young-Shin
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Department of Molecular Biology, Pusan National University, Busan, 609-735, Republic of Korea.
authors.forename: Mi-Ae
authors.initials: MA
authors.lastname: Yoo
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology / Q000378:metabolism*; D000375:Aging; D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism*; D007150:Immunohistochemistry; D007422:Intestines / Q000166:cytology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D064007:Ataxia Telangiectasia Mutated Proteins; C444435:Mei-41 protein, Drosophila; D017346:Protein Serine-Threonine Kinases; C514947:Tefu protein, Drosophila
keywords: ATM/ATR; DNA damage response; Drosophila; aging; intestinal stem cell