Characterization of Chromosome Fragile Sites in Yeast

描述(由申请人提供)：细胞保持完整或未断裂的染色体的能力对于正常的细胞生长和活力是必不可少的。然而，有一些染色体区域，称为染色体脆性部位，当细胞暴露在复制压力下时，很容易断裂。一旦被破坏，这些位置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。开发一种简单、易处理的真核细胞模型来研究染色体脆性部位对于未来的研究是必要的。这项建议旨在表征潜在的酵母脆弱部位，以确定哺乳动物和酵母脆弱部位之间的异同。不同的突变，一些提高遗传不稳定性，一些影响重组，对酵母脆性位点稳定性的影响也将被检测。此外，还提出了一种全基因组筛选的方法来鉴定酵母中新的染色体脆性部位。酵母染色体脆性位点模型系统的建立将促进基因组稳定性调控研究的发展，而基因组稳定性调控研究对于评价细胞转化和癌症的发展至关重要。

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.