HOMOLOGOUS RECOMBINATION IN LIVER REGENERATION

描述：同源重组(HR)是一种相对罕见的 哺乳动物细胞中的过程，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 发生在(脾和胸腺)。导致这一现象的分子机制 人力资源还没有得到很好的描述。只有两种哺乳动物的基因 已鉴定的与酵母中已鉴定的基因同源的基因 人力资源。此外，对细胞培养中HR活性的研究表明， 活性与转化的表型有关。初步数据 从申请人的实验室获得的核提取物表明，从 再生大鼠肝脏在纯化后催化同源重组(HR) 体外培养的质粒DNA底物。对照肝脏的核提取液是 没有这样的活动。因此，再生肝脏可能代表着一种独特的 正常哺乳动物细胞的心率调节模型。三个具体目标是 拟议研究的计划：(1)描述人力资源的变化 大鼠肝再生过程中细胞核提取物的活性，(2) 鉴定原代肝细胞培养中的HR活性，以及(3)鉴定 再生大鼠肝脏的HR组分。人物形象的塑造 肝脏再生的这些方面将为 哺乳动物同源重组蛋白的最终鉴定。

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.