Principal Investigator

George W. Teebor, M.D., Departments of Pathology and Environmental Medicine New York University School of Medicine

Ionizing radiation and chemical carcinogens can lead to the formation of clustered DNA damage, contributing to mutagenic, pre-cancerous or cancerous lesions. UV irradiated, gamma-irradiated and chemically oxidized DNA are substrates for the DNA repair activity of the enzyme Endonuclease III (Endo III). Endo III possesses DNA glycosylase and AP-lyase activities. Its DNA glycosylase activity releases pyrimidine hydrates from the DNA backbone, yielding apyrimidinic sites. Strand cleavage via beta-elimination of the 3'-phosphate group of the apyrimidinic sugar is effected by Endo III's AP-lyase activity.

Description of the Project
While bacterial Endo III has been well studied and characterized, to date no mammalian Endo III enzyme has been purified to homogeneity or cloned. The mammalian homolog of the DNA damage repair modulator Endo III has now been purified and the human gene cloned and characterized by Dr. Teebor and his laboratory. It is anticipated that having purified, cloned and active human enzyme may provide a means to treat the adverse effects of altered or deficient DNA repair mechanisms, exposure to radiation and oxidation, and cancerous or pre-cancerous conditions. For instance, UV Endo III activity is not detectable in Xeroderma pigmentosa cells and may contribute to its etiology. Therapeutically, cloned Endo III (or a modified form) may be valuable itself or in screening for drugs that modulate its activity. The now cloned and purified Endo III is also useful to monitor endogenous levels of the enzyme, detect increased sensitivity to DNA damage, and identify individuals at risk for radiation-induced DNA damage or cancer.

Applications
NYU is seeking an industrial partner(s) to assist in the commercial development of this technology for both diagnostic and therapeutic applications.

Patent Status
A patent application has been filed in the United States.

For further information please contact
New York University
Office of Industrial Liaison
650 First Avenue, New York, N.Y. 10016
Tel: (212)263-8178 Fax: (212)263-8189