Dr Jane Grasby

Dr Jane Grasby

Phone: 0114 22 29478
Room Number: C71

email : j.a.grasby@sheffield.ac.uk

Reader: BSc Birmingham (1988); PhD Southampton (1992); Research Fellow, Laboratory of Molecular Biology, Cambridge (1992-1994); Lecturer Sheffield (1994-99), Senior Lecturer Sheffield (1999-2002).

Key Words

Catalysis, protein and nucleic structure and function, nucleic acid chemistry, molecular recognition, enzymology

Research Interests

The interactions and reactions of nucleic acids are fundamental to all life processes. Our research seeks to gain understanding of these processes by exploiting the ability to synthesise chemically and modify nucleic acid structures. These studies include the interaction of proteins with both RNA and DNA and the interaction of nucleic acids with one another. In particular we are interested in the catalysis of reactions of nucleic acids by proteins and RNA enzymes (ribozymes). Currently we are undertaking both structural and mechanistic studies of an enzyme that catalyses the structure specific hydrolysis of nucleic acids (flap endonuclease), a ribozyme which specifically cleaves RNA and an enzyme that specifically catalyses the hydrolysis of DNA/RNA hybrid (RNase HII). Flap endonucleases and RNase HII are critical enzymes in DNA replication and repair.

A second area of research involves the combinational chemistry of nucleic acids. In collaboration with Dr D Williams we are synthesising modified nucleoside triphosphates to be used in the selection of novel nucleic acid catalytic activities.

Selected Publications

  • “Comparison of the catalytic parameters and reaction specificities of a phage and archaeal flap endonuclease”
    Ryan Willaims Blanka Sengerova, Sadie Osborne, Karl Syson, Sophie Ault, Anna Kilgour, Brian R Chapados, John A Tainer, Jon R Sayers, Jane A Grasby (2007) J. Mol. Biol. 371 34-48

  • “The pH dependence of Escherichia coli RNase HII-catalysed reaction suggests an active site carboxylate group participates directly in catalysis”
    James Bastock, Michelle Webb, Jane A Grasby (2007) J. Mol. Biol. 368 421-433

  • “The role of phosphate groups in the VS ribozyme substrate interaction.”
    Yana S Kovacheva, Svetomir B. Tzokov, Iain A. Murray, Jane A. Grasby (2004) Nucleic Acids Research 32, 6240-6250

  • “The synthesis and properties of oligoribonucleotide-spermine conjugates”
    Andrew J Marsh, David M Williams, Jane A Grasby (2004) Org. Biol. Chem. 2, 2103-2112

  • “Sequence-specific cleavage of RNA in the absence of divalent metal ions by a DNAzyme incorporating imidazolyl and amino functionalities.”
    Alexander Sidorov, Jane A Grasby and David M. Williams (2004), Nucleic Acids Research, 32, 1591-1601

  • “Determination of the catalytic parameters of the N-terminal half of Escherichia coli ribonuclease E and the identification of critical functional groups in RNA substrates”
    Yulia Redko Y, Mark R Tock, Christopher J Adams, VR Kaberdin, Jane A Grasby, Kenneth J McDowall (2003) J. Biol . Chem. 278 44001-44008 2003

  • “Dynamic Evidence for metal ion catalysis in the reaction mediated by a flap endonuclease “
    Mark R Tock, Elaine Frary, Jon R Sayers, Jane A Grasby (2003) EMBO J 22, 995-1004

  • "RNA footprinting analysis using ion pair reverse phase liquid chromatography". Mark J Dickman, Mathew J. Conroy, Jane A Grasby and David P Hornby RNA, 2002, 8, 247-251.

  • "Interactions of mutant and WT flap endonucleases with oligonucleotide substrates suggest an alternative model for DNA binding" Joe J Dervan, Min Feng, Dipak Patel, Jane A Grasby, Peter J Artymiuk, Thomas A Ceska and Jon R Sayers Proc. Natl. Acad. Sci. USA 2002, 99, 8542-8547

  • "A Conserved Tyrosine Residue Aids Ternary Complex Formation but not Catalysis, in Phage T5 Flap Endonuclease" Dipak Patel, Mark R Tock, Elaine Frary, Min Feng, Timothy J. Pickering, Jane A Grasby and Jon R. Sayers J. Mol. Biol., 2002, 320, 1025-1035.

  • "The role of magnesium ions and 2'-hydroxyl groups in the VS ribozyme-substrate interaction" Svetomir B. Tzokov, Iain A. Murray, Jane A. Grasby J. Mol. Biol. 2002, 324, 215-226.

  • "Enhancing the catalytic repertoire of nucleic acids. II.Simultaneous incorporation of amino and imidazolyl functionalities by two modified triphosphates during PCR" Thierry Gourlain, Alexander Sidorov, Nathalie Mignet, Simon J. Thorpe, Sarah E. Lee, Jane A. Grasby and David M. Williams, Nucleic Acids Research, 2001, 29, 1898-1905.

  • "Enhancing the catalytic repertoire of nucleic acids: a systematic study of linker length and rigidity" Sarah E. Lee, Alexander Sidorov, Thierry Gourlain, Nathalie Mignet, Simon J. Thorpe, John A. Brazier, Mark J. Dickman1, David P. Hornby1, Jane A. Grasby and David M. Williams Nucleic Acids Research, 2001, 29, 1565-1573.

  • "Novel syntheses of Z-alkene and alkane based modified nucleosides" Sarah E. Lee, Joseph S. Vyle, David M. Williams and Jane A. Grasby Tet. Lett., 2000, 41, 267-270.

  • "Variations in the Steady State Kinetic Parameters of Wild Type and Mutant T5 5’-3’ Exonuclease With pH; Protonation of Lys 83 is critical for DNA Binding" Timothy J. Pickering, Scott J. Garforth, Jon R. Sayers and Jane A. Grasby, J.Biol. Chem., 1999, 274, 17711-17717.

  • "A single cleavage Assay for T5 5Õ-3Õ Exonclease: - Determination of the Catalytic Parameters for Wild Type and Mutant Proteins" Timothy J. Pickering, Scott, J Garforth, Simon J. Thorpe, Jon R. Sayers and Jane A. Grasby, Nucleic Acids Res., 1999, 27,730-735.

  • "The role of Essential Pyrimidines in the Hairpin Ribozyme Catalysed Reaction", Karen J. Young, Joseph S Vyle, Timothy J. Pickering, Mark A. Cohen, Stephen C. Holmes, Olaf Merkel and Jane A. Grasby, J. Mol. Biol. 1999, 288, 853-866.

  • "Incorporation of Methylated PyrimidineAnalogues into RNA" Joseph S. Vyle, Karen J. Young and J A. Grasby, Tet. Lett., 1998, 39, 739, 5093-5096.

  • "Metal Ions Play a Passive Role in the Hairpin Ribzyme Reaction", K. Young, Francesca Gill and J.A. Grasby, Nucleic Acids Re., 1997, 25, 3760-3766.

  • "Purine Functional Groups in Essential Residues of the Hairpin Ribozyme Required for Catalytic Cleavage," J.A. Grasby, K. Mersmann, M. Singh, and M.J. Gait, Biochemistry, 1995, 34, 4068-4076.
See also