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Two ternary complexes of rat DNA polymerase β (pol β), a DNA template-primer, and dideoxycytidine triphosphate (ddCTP) have been determined at 2.9 Å and 3.6 Å resolution, respectively. ddCTP is the triphosphate of dideoxycytidine (ddC), a nucleoside analog that targets the reverse transcriptase of human immunodeficiency virus (HIV) and is at present used to treat AIDS. Although crystals of the two complexes belong to different space groups, the structures are similar, suggesting that the polymerase-DNA-ddCTP interactions are not affected by crystal packing forces. In the pol β active site, the attacking 3′-OH of the elongating primer, the ddCTP phosphates, and two Mg²⁺ ions are all clustered around Asp¹⁹⁰, Asp¹⁹², and Asp²⁵⁶. Two of these residues, Asp¹⁹⁰ and Asp²⁵⁶, are present in the amino acid sequences of all polymerases so far studied and are also spatially similar in the four polymerases—the …