Evolving contributions of the origin recognition complex (ORC) to subtelomeric chromatin

起源识别复合物 (ORC) 对亚端粒染色质的不断演变的贡献

• 批准号: 1615367
• 负责人: Laura Rusche
• 金额: $ 60万
• 依托单位: SUNY at Buffalo
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1615367&HistoricalAwards=false
• 关键词: Evolving; contributions; origin; recognition; complex

Gene duplication is a driving force in molecular evolution, as it provides new genetic material that can be adapted to serve different purposes in living organisms. This project is aimed at elucidating how duplicate genes diverge and their encoded proteins acquire distinct properties. In particular, the research will examine how a protein motif originally capable of one function can be adapted to perform other functions in the cell. The project is also designed to integrate research with training of undergraduate and graduate students who will gain hands-on experience in designing, executing, and interpreting experiments. In addition, a postdoctoral fellow who is planning a career in undergraduate education will gain teaching experience by coaching undergraduates in the laboratory, developing and implementing assessments for an undergraduate laboratory course, and designing and teaching a course during the three-week winter session. Finally, this project will enhance genetic resources for model organisms by developing additional yeast species for comparative evolutionary studies.The fates of duplicate genes are well-modeled theoretically. However, few studies of gene duplication move beyond sequence analysis to elucidate the changes that occur in protein function as duplicated genes diverge. The project will help fill this knowledge gap by tracing the evolution of two proteins that arose from subunits of the origin recognition complex (ORC). ORC promotes the assembly of a pre-replication complex for DNA synthesis, and five of its six subunits contain AAA+ domains that bind and hydrolyze ATP. In the budding yeast lineage, Orc1 duplicated to yield the heterochromatin protein Sir3, and Orc4 gave rise to the telomere-binding protein Rif2. Both Sir3 and Rif2 lack ATPase activity and have repurposed the AAA+ domain to bind other proteins. The research will compare the molecular properties of Orc1/Sir3 and Orc4/Rif2 in non-duplicated and duplicated yeast species, focusing on their protein interactions and genomic distributions. In addition, the contributions of these proteins to transcriptional repression and telomere length regulation will be examined. The findings will illustrate and clarify theoretical models of gene duplication by identifying how and when new protein functions arise.

基因复制是分子进化的驱动力，因为它提供了新的遗传物质，可以适应生物体的不同目的。该项目旨在阐明重复基因如何分化以及其编码的蛋白质如何获得不同的特性。特别是，该研究将研究最初能够实现一种功能的蛋白质基序如何适应细胞中的其他功能。该项目还旨在将研究与本科生和研究生的培训相结合，这些学生将获得设计，执行和解释实验的实践经验。此外，一个博士后谁是规划在本科教育的职业生涯将获得教学经验，辅导本科生在实验室，开发和实施本科实验室课程的评估，并设计和教学过程中为期三周的冬季会议。最后，本计画将借由开发额外的酵母物种以进行比较演化研究，来增加模式生物的遗传资源。然而，很少有研究基因复制超越序列分析，以阐明发生在蛋白质功能的变化，作为复制基因的分歧。该项目将通过追踪起源识别复合物（ORC）亚基产生的两种蛋白质的进化来填补这一知识空白。ORC促进DNA合成的复制前复合物的组装，其六个亚基中的五个含有结合和水解ATP的AAA+结构域。在芽殖酵母谱系中，Orc 1复制产生异染色质蛋白Sir 3，Orc 4产生端粒结合蛋白Rif 2。Sir 3和Rif 2都缺乏ATP酶活性，并重新利用AAA+结构域结合其他蛋白质。该研究将比较Orc 1/Sir 3和Orc 4/Rif 2在非复制和复制酵母物种中的分子特性，重点是它们的蛋白质相互作用和基因组分布。此外，这些蛋白质的转录抑制和端粒长度调节的贡献将被检查。这些发现将通过确定新蛋白质功能如何以及何时出现来阐明和澄清基因复制的理论模型。