HOMOLOGOUS RECOMBINATION IN LIVER REGENERATION

肝脏再生中的同源重组

• 批准号: 2114368
• 负责人: JENNIFER L CRUISE
• 金额: $ 10.02万
• 依托单位: UNIVERSITY OF ST. THOMAS
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-07-01 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2114368
• 关键词: DNA repair; antiserum; cell cycle; cell growth regulation; gene expression; gene targeting; genetic recombination; growth inhibitors; hepatectomy; laboratory rabbit; laboratory rat; liver cells; liver regeneration; nucleic acid biosynthesis; protein biosynthesis; protein purification; regulatory gene; tissue /cell culture

DESCRIPTION: Homologous recombination (HR) is a relatively infrequent process in mammalian cells, occurring primarily in meiotic tissues (testis and ovary) and tissues in which rearrangement of the immunoglobulin genes takes place (spleen and thymus). The molecular mechanisms responsible for HR have not been well characterized. Only two mammalian genes have been identified that exhibit homology to identified genes in yeast involved in HR. In addition, studies of HR activity in cell cultures indicate that the activity is associated with the transformed phenotype. Preliminary data from the applicant's laboratory indicate that nuclear extracts obtained from regenerating rat liver catalyze homologous recombination (HR) on purified plasmid DNA substrates in vitro. Nuclear extracts from control liver are without such activity. Regenerating liver may therefore represent a unique model of regulated HR in normal mammalian cells. Three specific aims are planned for the proposed study: (1) to characterize the changes in HR activity in nuclear extracts during rat liver regeneration, (2) to characterize HR activity in primary hepatocyte cultures, and (3) to identify the components of HR in regenerating rat liver. The characterization of these aspects of the liver regeneration will lay the groundwork for the eventual identification of mammalian proteins of homologous recombination.

描述：同源重组（HR）是一种相对罕见的 哺乳动物细胞中的一个过程，主要发生在减数分裂组织（睾丸 和卵巢）和免疫球蛋白基因重排的组织 发生（脾脏和胸腺）。 负责的分子机制 人力资源没有得到很好的描述。 只有两个哺乳动物基因 鉴定了与酵母中鉴定的基因具有同源性， HR. 此外，对细胞培养物中HR活性的研究表明， 活性与转化的表型相关。 初步数据 从申请人实验室获得的核提取物表明， 再生大鼠肝催化同源重组（HR）纯化 体外质粒DNA底物。 来自对照肝脏的核提取物是 没有这样的活动。 因此，再生肝脏可能代表了一种独特的 正常哺乳动物细胞中调节HR的模型。 三个具体目标是 拟定研究计划：（1）描述HR变化 大鼠肝再生过程中细胞核提取物的活性，（2） 表征原代肝细胞培养物中的HR活性，以及（3）鉴定 大鼠再生肝中HR的组成成分。 的表征 肝再生的这些方面将为 最终鉴定同源重组的哺乳动物蛋白质。