DNA Repair Enzyme.

About

Overview Ionizing radiation andchemical 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 repairactivity of the enzyme Endonuclease III (Endo III). Endo III possesses DNAglycosylase and AP-lyase activities. Its DNA glycosylase activity releasespyrimidine hydrates from the DNA backbone, yielding apyrimidinic sites. Strandcleavage via beta-elimination of the 3'-phosphate group of the apyrimidinic sugaris effected by Endo III's AP-lyase activity. Description of the Project While bacterial Endo IIIhas been well studied and characterized, to date no mammalian Endo III enzymehas been purified to homogeneity or cloned. The mammalian homolog of the DNA damagerepair modulator Endo III has now been purified and the human gene cloned andcharacterized by Dr. Teebor and his laboratory. It is anticipated that havingpurified, cloned and active human enzyme may provide a means to treat theadverse effects of altered or deficient DNA repair mechanisms, exposure toradiation and oxidation, and cancerous or pre-cancerous conditions. Forinstance, UV Endo III activity is not detectable in Xeroderma pigmentosa cellsand may contribute to its etiology. Therapeutically, cloned Endo III (or amodified form) may be valuable itself or in screening for drugs that modulateits activity. The now cloned and purified Endo III is also useful to monitorendogenous 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 anindustrial partner(s) to assist in the commercial development of thistechnology for both diagnostic and therapeutic applications.