MEC1-Dependent Redistribution of the Sir3 Silencing Protein from Telomeres to DNA Double-Strand Breaks

• Published in: Cell Vol. 97; no. 5; pp. 609 - 620
• Main Authors: Mills, Kevin D, Sinclair, David A, Guarente, Leonard
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 28.05.1999
• Subjects: Ataxia Telangiectasia - genetics; Ataxia Telangiectasia Mutated Proteins; Cell Cycle Proteins - metabolism; Chromatin - genetics; Chromatin - radiation effects; DNA Damage; DNA Repair - genetics; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Fungal Proteins - genetics; Fungal Proteins - metabolism; Gamma Rays; Heterochromatin - genetics; Heterochromatin - radiation effects; Histone Deacetylases; Humans; Intracellular Signaling Peptides and Proteins; Plasmids; Protein-Serine-Threonine Kinases; Proteins - genetics; Saccharomyces cerevisiae - cytology; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - radiation effects; Saccharomyces cerevisiae Proteins; Silent Information Regulator Proteins, Saccharomyces cerevisiae; Sirtuin 1; Sirtuin 2; Sirtuins; Telomere - genetics; Telomere - radiation effects; Trans-Activators - genetics; Trans-Activators - metabolism; Tumor Suppressor Proteins; Ultraviolet Rays
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/S0092-8674(00)80772-2

The yeast Sir2/3/4p complex is found in abundance at telomeres, where it participates in the formation of silent heterochromatin and telomere maintenance. Here, we show that Sir3p is released from telomeres in response to DNA double-strand breaks (DSBs), binds to DSBs, and mediates their repair, independent of cell mating type. Sir3p relocalization is S phase specific and, importantly, requires the DNA damage checkpoint genes MEC1 and RAD9. MEC1 is a homolog of ATM, mutations in which cause ataxia telangiectasia (A-T), a disease characterized by various neurologic and immunologic abnormalities, a predisposition for cancer, and a cellular defect in repair of DSBs. This novel mode by which preformed DNA repair machinery is mobilized by DNA damage sensors may have implications for human diseases resulting from defective DSB repair.