BIOLOGICAL FUNCTION OF MAMMALIAN TOPOISOMERASE II BETA

哺乳动物拓扑异构酶 II Beta 的生物学功能

• 批准号: 6180086
• 负责人: STEVEN D SHERIDAN
• 金额: $ 2.22万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6180086
• 关键词: DNA gyrase; developmental genetics; gene expression; genetic transcription; genetically modified animals; green fluorescent proteins; laboratory mouse; mammalian embryology; neurogenesis; protein isoforms; protein structure function

The main goal of this proposal is to answer the question why two typeII DNA topoisomerases with seemingly identical enzymatic properties are both needed in mammalian development. Under this central theme there are three specific aims. Aim I addresses the hypothesis that the activities are interchangeable but differences in temporal and/or tissue specific regulation of the topoisomerase II alpha and beta genes are responsible for the necessity of both. Aim II is directed at answering the question raised by the recent finding that inactivation of the beta isoform in the mouse prevents normal axon growth. A reporter gene (GFP) will be fused to topoisomerase II beta to allow detailed monitoring of this isoform during development. Finally, aim III addresses the hypothesis that the distinct C-terminal domain of the isoforms are responsible for their indispensability. This hypothesis will be tested through swapping of the C-terminal domain of one isoform by another.

这个建议的主要目标是回答这个问题，为什么两个II型DNA拓扑异构酶与看似相同的酶的性质都需要在哺乳动物的发展。 在这一中心主题下，有三个具体目标。 目的我地址的假设，活动是可互换的，但在时间和/或组织特异性调节的拓扑异构酶II α和β基因的差异是负责两者的必要性。 目的II是针对回答最近发现的问题，即小鼠中β亚型的失活会阻止正常轴突生长。 报告基因（GFP）将与拓扑异构酶II β融合，以便在发育期间详细监测该亚型。 最后，目的III解决了这样一个假设，即异构体的不同C-末端结构域是其不可或缺的原因。 将通过一种同种型的C-末端结构域与另一种同种型的C-末端结构域交换来检验该假设。