GENE EXPRESSION DURING THE CELL CYCLE

细胞周期中的基因表达

• 批准号: 2176636
• 负责人: NATHANIEL HEINTZ
• 金额: $ 27.48万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-07-01 至 1996-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2176636
• 关键词: DNA binding protein; DNA replication; Saccharomyces cerevisiae; cell cycle; cell growth regulation; chromosomes; fungal genetics; gene expression; genetic manipulation; genetic promoter element; genetic transcription; histones; human tissue; laboratory rabbit; molecular cloning; monoclonal antibody; nucleic acid sequence; phosphorylation; posttranslational modifications; protein kinase; synchronous cell division; tissue /cell culture; transcription factor

This proposal presents a series of focused studies to further elucidate the molecular basis for S phase specific transcription of histone genes, and to determine whether these mechanisms pertain in the regulation of chromosomal DNA synthesis. The ultimate aim of this work is to gain a molecular understanding of the transition from G1 to S phase, and to identify specific targets for intervention of cell growth at this point in the cell cycle. The experimental emphasis in this proposal is based on fundamental insights into this process gained during the last five years of this grant, and will focus upon six specific aims: 1) further characterization of the histone gene subtype specific cell cycle regulatory proteins OTF1, H1TF2, H1TF1 and H4TF2, 2) identification of enzymes involved in cell cycle regulated modification of OTF1, and demonstration that post- translational modification of OTF1 is functionally important for H2b transcription, 3) exploration of the regulation of H1TF2 (and ultimately H1TF1 and H4TF2) activity during the cell cycle to test whether the mechanisms regulating OTF1 are pleiotropic, 4) biochemical and genetic analysis of S. cerevisiae S phase specific histone gene transcriptional control, 5) analysis of the putative replication initiation factors RIP60 and RIP100 as potential substrates for the S phase regulatory mechanisms involved in transcriptional control, 6) analysis of upstream regulatory molecules in the pathway leading to activation of S phase specific transcription (e.g. protein phosphatase IIa, etc). These studies will result in identification of fundamental cell cycle regulatory mechanisms which may result in opportunities to specifically intervene in cell growth.

该提案提出了一系列重点研究，以进一步 阐明S相特异性转录的分子基础 组蛋白基因，并确定这些机制是否与 染色体DNA合成的调节。 最终目标 这项工作是为了获得对从 G1至s阶段，并确定干预的特定目标 细胞周期中的细胞生长。 实验 该提案的重点是基于对此的基本见解 在这笔赠款的最后五年中获得的过程，并将 关注六个具体目标：1）进一步表征 组蛋白基因亚型特异性细胞周期调节蛋白OTF1， H1TF2，H1TF1和H4TF2，2）鉴定涉及细胞的酶 周期调节OTF1的修饰，并证明 OTF1的翻译修改对于H2B在功能上很重要 转录，3）探索H1TF2的调节（和 最终在细胞周期期间的H1TF1和H4TF2）活性 调节OTF1的机制是否为多效性，4） 酿酒酵母特异性的生化和遗传分析 组蛋白基因转录控制，5）推定的分析 复制启动因子RIP60和RIP100作为潜力 S相调节机制的底物 转录控制，6）上游调节分子的分析 在导致S相特异性激活的途径中 转录（例如蛋白质磷酸酶IIA等）。 这些研究 将导致鉴定基本细胞周期调节 可能导致机会专门的机制 干预细胞生长。