The aim of this project is to examine the involvement of certain ribonucleases in cellular events. The scope of this project has evolved to include protein chemistry, enzymatic activity, overproduction of proteins and the consequences of changes in the level of enzymatic activity within the cell. In particular, ribonucleases specific for RNA of RNA-DNA hybrids are being examined for their functional role within the cell. Multiple enzymes exhibiting RNase H activity have been reported within cells and our experiments are aimed at understanding the need for multiple forms of the enzyme and what effects there would be upon inhibition of each (or all) of the RNase H activities. This is particularly relevant since the AIDS virus requires the functioning of its own RNase H to be infectious.
| Nowotny, Marcin; Gaidamakov, Sergei A; Ghirlando, Rodolfo et al. (2007) Structure of human RNase H1 complexed with an RNA/DNA hybrid: insight into HIV reverse transcription. Mol Cell 28:264-76 |
| Budihas, Scott R; Gorshkova, Inna; Gaidamakov, Sergei et al. (2005) Selective inhibition of HIV-1 reverse transcriptase-associated ribonuclease H activity by hydroxylated tropolones. Nucleic Acids Res 33:1249-56 |
| Gaidamakov, Sergei A; Gorshkova, Inna I; Schuck, Peter et al. (2005) Eukaryotic RNases H1 act processively by interactions through the duplex RNA-binding domain. Nucleic Acids Res 33:2166-75 |
| Nowotny, Marcin; Gaidamakov, Sergei A; Crouch, Robert J et al. (2005) Crystal structures of RNase H bound to an RNA/DNA hybrid: substrate specificity and metal-dependent catalysis. Cell 121:1005-16 |
| Chan, King C; Budihas, Scott R; Le Grice, Stuart F J et al. (2004) A capillary electrophoretic assay for ribonuclease H activity. Anal Biochem 331:296-302 |
| Jeong, Ho-Sang; Backlund, Peter S; Chen, Hao-Chia et al. (2004) RNase H2 of Saccharomyces cerevisiae is a complex of three proteins. Nucleic Acids Res 32:407-14 |
| Broccoli, Sonia; Rallu, Fabien; Sanscartier, Patrick et al. (2004) Effects of RNA polymerase modifications on transcription-induced negative supercoiling and associated R-loop formation. Mol Microbiol 52:1769-79 |
| Backer, Marina V; Gaynutdinov, Timur I; Gorshkova, Inna I et al. (2003) Humanized docking system for assembly of targeting drug delivery complexes. J Control Release 89:499-511 |
| Pileur, Frederic; Andreola, Marie-Line; Dausse, Eric et al. (2003) Selective inhibitory DNA aptamers of the human RNase H1. Nucleic Acids Res 31:5776-88 |
| Cerritelli, Susana M; Frolova, Ella G; Feng, Chiguang et al. (2003) Failure to produce mitochondrial DNA results in embryonic lethality in Rnaseh1 null mice. Mol Cell 11:807-15 |
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