| Title | Drosophila atm/telomere fusion is required for telomeric localization of HP1 and telomere position effect. | | Author(s) | Oikemus SR, McGinnis N, Queiroz-Machado J, Tukachinsky H, Takada S, Sunkel CE, Brodsky MH | | Institution | Program in Gene Function and Expression and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA. | | Source | Genes Dev 2004 Aug 1; 18(15):1850-61. | | MeSH | Animals
Animals, Genetically Modified
Apoptosis
Ataxia Telangiectasia
Base Sequence
Cell Cycle
Cell Cycle Proteins
Chromosomal Proteins, Non-Histone
Chromosomes
Comparative Study
DNA Damage
DNA-Binding Proteins
Drosophila melanogaster
In Situ Hybridization, Fluorescence
Molecular Sequence Data
Mutation
Protein-Serine-Threonine Kinases
Research Support, Non-U.S. Gov't
Sequence Homology, Nucleic Acid
Telomere
Terminal Repeat Sequences
Tumor Suppressor Protein p53
Tumor Suppressor Proteins
| | Abstract | Terminal deletions of Drosophila chromosomes can be stably protected from end-to-end fusion despite the absence of all telomere-associated sequences. The sequence-independent protection of these telomeres suggests that recognition of chromosome ends might contribute to the epigenetic protection of telomeres. In mammals, Ataxia Telangiectasia Mutated (ATM) is activated by DNA damage and acts through an unknown, telomerase-independent mechanism to regulate telomere length and protection. We demonstrate that the Drosophila homolog of ATM is encoded by the telomere fusion (tefu) gene. In the absence of ATM, telomere fusions occur even though telomere-specific Het-A sequences are still present. High levels of spontaneous apoptosis are observed in ATM-deficient tissues, indicating that telomere dysfunction induces apoptosis in Drosophila. Suppression of this apoptosis by p53 mutations suggests that loss of ATM activates apoptosis through a DNA damage-response mechanism. Loss of ATM reduces the levels of heterochromatin protein 1 (HP1) at telomeres and suppresses telomere position effect. We propose that recognition of chromosome ends by ATM prevents telomere fusion and apoptosis by recruiting chromatin-modifying complexes to telomeres. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 15256487 |
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