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: 2459278
• 负责人: Orna Cohen-Fix
• 金额: $ 2.99万
• 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: 1997-08-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2459278
• 关键词: Saccharomyces cerevisiae; alleles; cell cycle proteins; cell growth regulation; fungal genetics; mitotic spindle apparatus; transcription factor

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.

在有丝分裂期间，染色体以极高的保真度分离。 这是 通过将配对的姐妹染色单体附着到双极来实现 纺锤体以及称为检查点的调节机制的存在， 在 DNA 或纺锤体损伤的情况下抑制有丝分裂。损失 这些调节机制，如某些类型的癌症中所发生的那样， 导致染色体错误分离，进而导致总细胞 缺陷和细胞死亡。实现有丝分裂的分子机制 被捕情况仍不明。最近，一个基因编码了一个假定的 有丝分裂抑制剂，称为 PDS1，已在酵母中被发现 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 逮捕，并且它们有纺锤体伸长缺陷。 Pds1p 似乎是 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，其降解使有丝分裂得以进行。 Pds1p 在有丝分裂调节中的作用将通过 检查 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 的作用 执行有丝分裂能力的导数，并通过确定作用 APC 和 Pds1p 降解中其他降解相关因素的影响。 可能与 Pds1p 相互作用的蛋白质将通过 筛选条件 pds1 等位基因的基因外抑制子。这 Pds1p 参与纺锤体功能和有丝分裂的可能性 源自两种不同功能的监管将由 试图生成 pds1 等位基因，其中任一 功能。这些实验的结果不仅将揭示 Pds1p 功能以及姐妹染色单体的分子机制 内聚力、DNA 损伤检查点和纺锤体伸长。