Characterization of Chromosome Fragile Sites in Yeast

酵母染色体脆弱位点的表征

• 批准号: 7058019
• 负责人: Francene J. Lemoine
• 金额: $ 2.55万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-01-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7058019
• 关键词: DNA damage; DNA replication; Saccharomyces cerevisiae; cell component structure /function; chromosome disorders; chromosome movement; fungal genetics; gene mutation; postdoctoral investigator

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.

描述（由申请人提供）：细胞保持完整或不间断的染色体的能力对于正常的细胞生长和生存能力至关重要。但是，有些染色体区域，称为染色体脆弱的部位，当细胞暴露于复制应力时，它们容易断裂。一旦破碎，这些位点通常参与易位和其他基因组重排，这些重排是某些人类肿瘤的特征。对于将来的研究，必须开发用于染色体脆弱部位的简单，可易处理的真核模型。该建议旨在表征潜在的酵母菌部位，以识别哺乳动物和酵母脆弱部位之间的相似性和差异。还将检查各种突变的影响，有些突变升高遗传不稳定性和一些影响重组的影响，对酵母脆弱的位点稳定性也将进行检查。此外，提出了用于鉴定酵母中新型染色体脆弱位点的全基因组筛查。建立酵母染色体脆弱的现场模型系统将允许基因组稳定性调节研究的发展，这对于欣赏细胞转化和癌症发展至关重要。