Title

Drosophila atm/telomere fusion is required for telomeric localization of HP1 and telomere position effect

UMMS Affiliation

Graduate School of Biomedical Sciences; Program in Gene Function and Expression; Program in Molecular Medicine

Date

7-17-2004

Document Type

Article

Medical Subject Headings

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 Proteins

Disciplines

Life Sciences | Medicine and Health Sciences

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.

Rights and Permissions

Citation: Genes Dev. 2004 Aug 1;18(15):1850-61. Epub 2004 Jul 15. Link to article on publisher's site

Related Resources

Link to article in PubMed