Genetic and Biochemical Studies of Ribonucleases H

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Ribonuclease H (RNase H) genes and/or their activities have been identified in all systems studied to date ranging from archaebacteria to man. This suggests that they may be one of a limited number of activities required for minimal biological life. Multiple RNase H isoforms exist in prokaryotes and eukaryotes and all known for their ability to degrade the RNA strands of RNA:DNA heteroduplexes. This simple function implicates the enzymes in regulating RNA:DNA duplex formation during DNA replication, RNA transcription, chromatin ultrastructure and viral and cellular reverse transcription. The existence of multiple RNase H isoforms also suggest that what is learned of isoforms in one system may relate to our understanding of isoform structure and function elsewhere. The studies described here are broadly significant in scope, impacting conserved and novel roles for ribonucleases H in all biological systems. Furthermore,they exploit the genetics of Trypanosoma brucei, a system that has been the prototype for unmasking unusual nucleic acid metabolic events such as RNA editing and RNA trans-splicing.