The ability of a cell to maintain intact, or unbroken, chromosomes is essential for normal cellular growth and viability. However, there are certain chromosomal regions, known as chromosome fragile sites, which are prone to breakage when cells are exposed to replication stresses. Once broken, these sites often are involved in translocations and other genome rearrangements which are characteristic of some human tumors. The development of a simple, tractable eukaryotic model for chromosome fragile sites is necessary for future studies. This proposal is designed to characterize a potential yeast fragile site to identify similarities and differences between mammalian and yeast fragile sites. The effects of various mutations, some that elevate genetic instability and some that affect recombination, on yeast fragile site stability also will be examined. Additionally, a genome-wide screen for the identification of novel chromosome fragile sites in yeast is proposed. The establishment of a yeast chromosome fragile site model system will allow for the advancement of genome stability regulation studies, which are critical to the appreciation of cellular transformation and cancer development. ? ?
