Drosophila atm/telomere fusion is required for telomeric localization of HP1 and telomere position effect
Authors
Oikemus, Sarah R.Schultz, Nadine
Queiroz-Machado, Joana
Tukachinsky, Hanna
Takada, Saeko
Sunkel, Claudio E.
Brodsky, Michael H.
UMass Chan Affiliations
Program in Molecular MedicineProgram in Gene Function and Expression
Graduate School of Biomedical Sciences
Document Type
Journal ArticlePublication Date
2004-07-17Keywords
Animals; Animals, Genetically Modified; Apoptosis; Ataxia Telangiectasia; Base Sequence; Cell Cycle; Cell Cycle Proteins; Chromosomal Proteins, Non-Histone; Chromosomes; DNA Damage; DNA-Binding Proteins; Drosophila melanogaster; In Situ Hybridization, Fluorescence; Molecular Sequence Data; Mutation; Protein-Serine-Threonine Kinases; Sequence Homology, Nucleic Acid; Telomere; Terminal Repeat Sequences; Tumor Suppressor Protein p53; Tumor Suppressor ProteinsLife Sciences
Medicine and Health Sciences
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Show full item recordAbstract
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.Source
Genes Dev. 2004 Aug 1;18(15):1850-61. Epub 2004 Jul 15. Link to article on publisher's siteDOI
10.1101/gad.1202504Permanent Link to this Item
http://hdl.handle.net/20.500.14038/34264PubMed ID
15256487Related Resources
Link to article in PubMedae974a485f413a2113503eed53cd6c53
10.1101/gad.1202504
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