Research into telomere maintenance is at the forefront of the biomedical investigation of aging and cancer. Telomeres, the specialized ends of eukaryotic chromosomes, are required for normal cell growth. Recently, a collaboration of scientists from around the country has discovered a key component in the mammalian telomere maintenance machinery. As reported in Genes & Development, Hsu and colleagues have found that the protein Ku mediates mammalian telomere capping.
Telomere capping conceals and disguises the ends of chromosomal DNA so to distinguish it from double stranded DNA breaks. Telomere capping thereby prevents the fusion of chromosome ends, an event associated with genetic instability and a hallmark in the development of cancer. The association of Ku with the mammalian telomere was, though, a surprising discovery.
Ku was originally discovered as a member of the DNA damage repair complex which repairs double stranded DNA breaks. One would expect that such proteins would be excluded from the telomeres, but that is not the case. Hsu and colleagues determined that Ku acts in a unique way at the mammalian telomere. Ku specifically binds a telomere binding protein, and is required to prevent telomere end fusion. Mouse cells that lack Ku develop numerous chromosome fusions.
Ku works at the mammalian telomere in a functionally distinct manner from its action at double stranded breaks. Understanding the surprising association of Ku with the mammalian telomere is a primary step in understanding the delicate balance of cellular growth control and the aberrations which lead to cancer.
Genes & Development