PDS1, A REGULATOR OF MITOSIS IN BUDDING YEAST

PDS1，芽殖酵母有丝分裂的调节因子

• 批准号: 2173254
• 负责人: Orna Cohen-Fix
• 金额: $ 2.37万
• 依托单位: CARNEGIE INSTITUTION OF WASHINGTON, D.C.
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-01-02 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2173254
• 关键词: PDS1; REGULATOR; MITOSIS; BUDDING; YEAST

During mitosis, chromosomes segregate with exquisite fidelity. This is achieved by the attachment of paired sister chromatids to the bipolar spindle and by the presence of regulatory mechanisms, called checkpoints, that inhibit mitosis in the presence of DNA or spindle damage. The loss of these regulatory mechanisms, as occurs in certain types of cancer, leads to chromosome missegregation that in turn results in gross cellular defects and cell death. The molecular mechanism that enables mitotic arrest is still unknown. Recently, a gene encoding for a putative inhibitor of mitosis, called PDS1, has been identified in the yeast Saccharomyces cerevisiae. In the absence of PDS1, sister chromatids separate prematurely, cells fail to exhibit a DNA damage checkpoint arrest, and they have a spindle elongation defect. Pds1p appears to be a substrate of the anaphase promoting complex (APC), which is involved in the degradation of type-B cyclins. These results suggest that Pds1p in an inhibitor of mitosis and that its degradation allows mitosis to proceed. The role of Pds1p in the regulation of mitosis will be studied by examining the expression pattern and cellular localization of Pds1p during the cell cycle, by studying the effect of a non-degradable Pds1p derivative on the ability to execute mitosis, and by determining the role of APC and other degradation-associated factors in Pds1p degradation. Proteins that potentially interact with Pds1p will be identified by screening for extragenic suppressors of conditional pds1 alleles. The possibility that the involvement of Pds1p in spindle function and mitotic regulation stems from two different functions will be examined by attempting to generate pds1 alleles specifically defective in either function. The results of these experiment will shed light not only on Pds1p function but also on the molecular mechanisms of sister chromatid cohesion, DNA damage checkpoint and spindle elongation.

在有丝分裂过程中，染色体精确地分离。 这是 通过将成对的姐妹染色单体连接到双极 纺锤体和调节机制的存在，称为检查点， 在DNA或纺锤体损伤的情况下抑制有丝分裂。损失 在这些调节机制中，就像某些类型的癌症中发生的那样， 导致染色体的错误分离，进而导致细胞内的 缺陷和细胞死亡。有丝分裂的分子机制 逮捕仍然未知。最近，一个编码一种假定的 有丝分裂的抑制剂，称为PDS1，已经在酵母中鉴定出 酿酒酵母在没有PDS1的情况下，姐妹染色单体 过早分离，细胞无法表现出DNA损伤检查点， 停止，并且它们具有纺锤体伸长缺陷。Pds1p似乎是一个 后期促进复合物（APC）的底物，参与 B型细胞周期蛋白的降解。这些结果表明，Pds1p在 有丝分裂抑制剂，其降解允许有丝分裂进行。 Pds1p在有丝分裂调节中的作用将通过以下方法进行研究： 检测Pds1p的表达模式和细胞定位 在细胞周期中，通过研究不可降解的Pds1p 衍生物的能力，执行有丝分裂，并通过确定的作用， APC和其他降解相关因子在Pds1p降解中的作用。 可能与Pds1p相互作用的蛋白质将通过以下方法鉴定： 筛选条件链1等位基因的基因外抑制子。的 Pds1p可能参与纺锤体功能和有丝分裂 监管源于两个不同的职能将审查 试图产生特异性缺陷于 功能这些实验的结果不仅将揭示 Pds1p功能以及对姐妹染色单体的分子机制 内聚、DNA损伤检查点和纺锤体延伸。