Screen for novel protein inhibitors based upon engineered...

Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid

Reexamination Certificate

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C435S252330

Reexamination Certificate

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07867702

ABSTRACT:
The present invention provides a method for identifying the presence of a protein inhibitor of a target protein in a sample, comprising the steps of a) contacting said sample with a cell, wherein said cell contains i) an inducible lethal overactivity mutation in a gene affecting the target protein; and ii) a mutation in a second gene, wherein the activity of the target protein is essential to the cell and the mutation in the second gene functionally compensates for any reduction in the activity of the target protein; b) inducing the lethal overactivity mutation; and subsequently c) assessing protein inhibition by comparing the degree of survival of the cell in the presence and the absence of said sample. Also provided are cells for use in said method.

REFERENCES:
patent: 2002/0022718 (2002-02-01), Forsyth et al.
patent: 2002/0045592 (2002-04-01), Zyskind et al.
patent: WO 97/43727 (1997-12-01), None
Boye, E. et al. (2000) “Limiting DNA replication to once and only once” EMBO Reports 1:479-483.
Erzberger, J.P. et al. (2002) “The structure of bacterial DnaA: implications for general mechanisms underly8ing DNA replication initiation” The EMBO Journal 21:4763-4773.
Giraldo, R. et al. (2001) “Similarities between the dna replication initiators of gram-negative bacteria plasmids (RepA) and eukaryotes (Orc4p)/archaea (Cdc6p)” PNAS 98:4938-4943.
Hansen, F. et al. (1995) “Initiation of chromosome replication after induction of DnaA protein synthesis in a dnaA(null) rnh mutant ofEscherichia coli” Molecular Microbiology 15:149-154.
Hansen, F.G. et al. (1992) “Cloning and nucleotide sequence determination of twelve mutant dnaA genes ofEscherichia coli” Mol. Gen. Genet. 234:14-21.
Hirota, Y. et al. (1970) “On the process of cellular division inEscherichia coli. III. Thermosensitive mutants ofEscherichia colialtered in the process of dna initiation” J. Mol. Biol. 53:369-387.
Itaya, M. et al. (1991) “Correlation of activity with phenotypes ofEscherichia colipartial function mutants of rnh, the gene encoding RNase H” Mol. Gen. Genet. 227:433-437.
Katayama, T. (2001) “Feedback controls restrain the initiation ofEscherichia colichromosomal replication” Molecular Microbiology 41:9-17.
Katayama, T. et al. (1994) “Hyperactive initiation of chromosomal replication in vivo and in vitro by a mutant initiator protein, DnaAcos, ofEscherichia coli” Journal of Biological Chemistry 269:12698-12703.
Katayama, T. et al. (1995) “Characterization ofEscherichia coliDnaAcos protein in replication systems reconstituted with highly purified proteins” Molecular Microbiology 18:813-820.
Katayama, T., et al. (1997) “CedA is a novelEscherichia coliprotein that activates the cell division inhibited by chromosomal dna over-replication” Molecular Microbiology 26:687-697.
Kellenberger-Gujer, G. et al. (1978) “A cold sensitive dnaA mutant ofE. coliwhich overinitiates chromosome replication at low temperature” Molec. Gen. Genet. 162:9-16.
Kogoma, T. et al. (1983) “The origin of replication, oriC, and the dnaA protein are dispensable in stable DNA replication (sdrA) mutants ofEscherichia coliK-12” The EMBO Journal 2:463-468.
Kohiyama, M. (1968) “DNA synthesis in temperature sensitive mutants ofEscherichia coli” Cold Spring Harb. Symp. Quant. Biol. 33:317-324.
Liang, C. et al. (1995) “ORC and Cdc6p interact and determine the frequency of initiation of dna replication in the genome” Cell 81:667-676.
Liang, C. et al. (1997) “Persistent initiation of DNA replication and chromatin-bound MCM proteins during the dell cycle in cdc6 mutants” Genes & Development 11:3375-3386.
Liu, J. et al. (2000) “Structure and function of Cdc6/Cdc18: implications for origin recognition and checkpoint control” Molecular Cell 6:637-648.
Muzi-Falconi, M. et al. (1996) “cdc18+ regulates initiation of dna replication in schizosaccharomyces pombe” PNAS USA 93:1566-1570.
Nishitani, H. et al. (1995) “p65cdc18plays a major role controlling the initiation of dna replication in fission yeast” Cell 83:397-405.
Sekimizu, K. et al. (1987) “ATP activates dnaA protein in initiating replication of plasmids bearing the origin of theE. colichromosome” Cell 50:259-265.
Shinpuku, T. et al. (1995) “Phenotypes of dnA mutants ofEscherichia colisensitive to detergents and organic solvents” Biochemical and Biophysical Research Communications 212:84-89.
Shrager, J. et al. (2001) “High throughput discovery: search and interpretation on the path to new drugs” In K. Crowley, et al. (Eds.) Design for Science. Hillsdale, NJ: Lawrence Erlbaum, pp. 325-348.
Skarstad, K. et al. (1994) “The initiator protein DnaA: evolution, properties and function” Biochimica et Biophysical Acta 1217:111-130.
Von Meyenburg, K. et al. (1987) “Mode of initiation of constitutive stable dna replication in RNase h-defective mutants ofEscherichia coliK-12” J. of Bacteriology 169:2650-2658.
Wei, M.H. (2000) “Discovery of novel antibiotics: application of structural and functional genomics” http://bioinfo.mbb.yale.edu/mbb452a/2000/projects/Marlynn-H-Wei.html.
Weigel, C. et al. (1999) “The n-terminus promotes oligomerization of theEscherichia coliinitiator protein DnaA” Molecular Microbiology 24:53-66.
Itaya, M. et al. 1999 “Isolation of RNase H genes that are essential for growth ofBacillus subtilis168”J Bacteriol181:2118-2123.
Kato, J and Katayama, T. 2001 “Hda, a novel DnaA-related protein, regulates the replication cycle inEscherichia coli” The EMBO J20:4253-4262.
Ogawa, T, et al. 1984 “RNase H confers specificity in the dnaA-dependent initiation of replication at the unique origin ofEscherichia colichromosome in vivo and in vitro”Proc Natl Acad Sci USA81:1040-1044.
Von Meyenburg, K et al. 1987 “Mode of initiation of constitutive stable DNA replication in RNase H-defective mutants ofEscherichia coliK-12”J Bacteriol169:2650-2658.

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