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The Drosophila ATM ortholog, dATM, mediates the response to ionizing radiation and to spontaneous DNA damage during development.

Song, YH, Mirey, G, Betson, M, Haber, DA and Settleman, J (2004) The Drosophila ATM ortholog, dATM, mediates the response to ionizing radiation and to spontaneous DNA damage during development. Curr Biol, 14 (15). pp. 1354-1359.

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Cells of metazoan organisms respond to DNA damage by arresting their cell cycle to repair DNA, or they undergo apoptosis. Two protein kinases, ataxia-telangiectasia mutated (ATM) and ATM and Rad-3 related (ATR), are sensors for DNA damage. In humans, ATM is mutated in patients with ataxia-telangiectasia (A-T), resulting in hypersensitivity to ionizing radiation (IR) and increased cancer susceptibility. Cells from A-T patients exhibit chromosome aberrations and excessive spontaneous apoptosis. We used Drosophila as a model system to study ATM function. Previous studies suggest that mei-41 corresponds to ATM in Drosophila; however, it appears that mei-41 is probably the ATR ortholog. Unlike mei-41 mutants, flies deficient for the true ATM ortholog, dATM, die as pupae or eclose with eye and wing abnormalities. Developing larval discs exhibit substantially increased spontaneous chromosomal telomere fusions and p53-dependent apoptosis. These developmental phenotypes are unique to dATM, and both dATM and mei-41 have temporally distinct roles in G2 arrest after IR. Thus, ATM and ATR orthologs are required for different functions in Drosophila; the developmental defects resulting from absence of dATM suggest an important role in mediating a protective checkpoint against DNA damage arising during normal cell proliferation and differentiation.

Item Type: Article
Divisions : Surrey research (other units)
Authors :
Song, YH
Mirey, G
Haber, DA
Settleman, J
Date : 10 August 2004
DOI : 10.1016/j.cub.2004.06.064
Uncontrolled Keywords : Animals, Apoptosis, Ataxia Telangiectasia Mutated Proteins, Blotting, Northern, Cell Cycle Proteins, DNA Damage, DNA-Binding Proteins, Drosophila, Drosophila Proteins, Eye, Female, Fertility, Gene Expression Regulation, Developmental, In Situ Nick-End Labeling, Larva, Microscopy, Electron, Scanning, Mitosis, Phylogeny, Protein Structure, Tertiary, Protein-Serine-Threonine Kinases, Tumor Suppressor Proteins, Wings, Animal, X-Rays
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 10:33
Last Modified : 24 Jan 2020 19:34

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