Telomeres are defined as the ends of chromosomal DNA and are essential for the faithful inheritance and stability of chromosomes. The enzyme telomerase is necessary for telomere maintenance, thus the mechanisms of DNA recognition and synthesis by telomerase, and the cellular patterns of telomerase expression and regulation are essential for a complete understanding of telomere biology. The structure and length of telomeres, parameters which may determine the proliferative lifespan of cells, is regulated by controlling the activity and expression of telomerase. By identifying telomerase components and using them as markers to track telomerase expression, the relationships between cell division and telomere function can be defined. Human telomerase is a ribonucleoprotein, its essential RNA moiety will be identified with polymerase chain reaction amplification techniques. The RNA sequence is critical to understanding the telomerase reaction mechanism, since it is believed to contain a sequence that templates telomeric repeat synthesis. Conserved features of the RNA will be elucidated by comparing the gene sequence from a variety of vertebrates, the importance of RNA structures and sequences will be tested by expressing altered telomerase RNA genes in cell lines. %%% Chromosomes carry the genetic blueprint that is used by all multicellular organisms from worms to humans to make organs, muscles, skin, etc. An enzyme in these organisms is responsible for adding special nucleic acid sequences at the end of each of the chromosomes that is necessary for their stability. This is important for chromosomes in sperm and egg cells but also for cells of the body. These sequences may be important in the development of cells into tissues and whether the cells live or die during the life of the organism. The structure of the enzyme which contains both nucleic acid and amino acids is not understood; the gene for the enzyme has not as yet been found. These two aims will be investigated by the laboratory.
