Protein phosphorylation has long been recognized as a major mechanism in mediating cellular responses to environmental conditions. Protein phosphorylation is central to signal transduction pathways and cell cycle regulation. DNA-Dependent Protein Kinase (DNA-PK) is a nuclear threonine-serine protein kinase involved in DNA double-stranded break repair and V(D) J recombination. The present invention provides tools for monitoring the activity of the enzyme in cells, providing highly specific peptide substrates and nucleic acid cofactors in addition to genetic constructs for expression of protein substrates.
The role of this enzyme in the regulation of cell growth and in the development of immunity makes this assay a potent tool for assessing the efficacy of effector molecules. Drugs that alter the DNA-PK activity of cells might be used in the design of new anticancer chemotherapeutic strategies such as the development of agents that potentiate the effect of chemotherapeutic drugs so as to make them less toxic to noncancerous tissue. Effectors of DNA-PK activity might also be used as therapeutic modulators in the treatment of various disorders of the immune system.
The materials disclosed in the present invention provide immediate access to determining the status of the DNA-PK activity in living cells. The disclosures include methods for identifying agents that specifically alter the activity of this critical cellular enzyme. License Status: Available on a negotiable basis.
More info: Christine Brakel at brakel@bnl.gov