A full-length cDNA sequence encoding TC3 has been determined. TC3 mRNA is overexpressed in 38 out of 40 cases of surgically removed, human colorectal carcinomas examined, but not in the adjacent normal colonic epithelia. In addition to colorectal cancers from surgery, overexpression of TC3 mRNA or protein is also observed in most of human cancer cell lines and various tumorigenic rodent cell lines examined, but only rarely in cell strains or lines derived from normal tissues. TC3 shares sequence homologies with RuvB, a DNA helicase involved in recombinational repair of E. coli, and SV4O T antigen, a p53-binding helicase. TC3 is inducible by UV light, confers increased UV-resistance, and binds p53. We wish to characterize TC3 further to facilitate our understanding on the origin and consequence of TC3 overexpression in human colorectal cancers by molecular and cellular approaches. We will identify its DNA-binding site, oligomerization domain, and p53-binding domain. We will examine the consequences of inactivation of TC3 expression in human colorectal carcinoma cell lines by antisense approach and by homologous recombination. We will isolate TC3 complexes and characterize its components.
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