Telomeres are the DNA-protein complexes that form the ends of eukaryotic linear chromosomes and protect their integrity. Telomeres are a focus of research on aging (which is accompanied by gradual telomere loss) and tumorigenesis (which requires stabilization of telomere length). Recent work suggests that telomeres might play roles in sexual reproduction as well, as they become associated with the spindle pole bodies (SPBs) and lead chromosome movements during pre-meiotic stages in fission yeast. The fission yeast telomere protein Taz1 is a key regulator of telomere length, structure and position effects, but is critical for viability only in cells that have initiated the sexual cycle. Indeed, Taz1p is required for pre-meiotic telomere clustering at the SPBs, the absence of which leads to aberrant meiotic recombination and segregation. Taz1p is the first protein shown to be involved in telomere-SPB associations and thus provides an unprecedented foothold for studying the mechanisms underlying meiotic chromosomal rearrangements and the roles of these rearrangements in sexual development. The proposed work addresses five questions, using cytological, molecular genetic, and physiological approaches: (1) What is the role of telomere clustering at SPBs during meiosis and what processes depend on pre-meiotic chromosomal alignment? (2) What are the signals that lead from the pheromone response to the pre-meiotic chromosomal rearrangements? (3) Under what conditions is Taz1p important for mitotic growth and what role does it play under such conditions? (4) As a corollary to 2 and 3, is Taz1p regulated by phosphorylation? (5) What proteins interact with Taz1p to mediate or participate in its meiotic function? These studies will greatly expand our knowledge of telomere function during sexual reproduction and under stress. Given that telomere culstering during meiosis has been observed in many eukaryotes, and that the human telomere protein hTRF1 is structurally and functionally homologous to Taz1p these studies should also illuminate processes involved in human meiosis.
