Characterization of Chromosome Fragile Sites in Yeast

描述（由申请方提供）：细胞保持染色体完整或不断裂的能力对于正常细胞生长和活力至关重要。然而，有某些染色体区域，称为染色体脆性位点，当细胞暴露于复制应激时，这些区域易于断裂。一旦被破坏，这些位点通常涉及易位和其他基因组重排，这是一些人类肿瘤的特征。建立一个简单、易操作的真核细胞染色体脆性位点模型对今后的研究具有重要意义。该建议旨在表征一个潜在的酵母脆性位点，以确定哺乳动物和酵母脆性位点之间的相似性和差异。各种突变的影响，一些提高遗传不稳定性和一些影响重组，对酵母脆性位点的稳定性也将进行检查。此外，提出了一个全基因组筛选酵母中新的染色体脆性位点的鉴定。酵母染色体脆性位点模型系统的建立将推动基因组稳定性调控研究的进展，这对于理解细胞转化和癌症发展至关重要。

DESCRIPTION (provided by applicant): 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.