HOMOLOGOUS RECOMBINATION IN LIVER REGENERATION

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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.