Interaction of Escherichia coli UvrABC nuclease with DNA adducts formed by (+)anti- and (+)syn-benzo(a)pyrene diol epoxide

The polycyclic aromatic hydrocarbon (+)anti-benzo(a)pyrene diol epoxide (BPDE+2) is carcinogenic, while (+)-syn-benzo(a)pyrene diol epoxide (BPDE+1) is not. They bind to DNA to form the trans-dG-adduct for BPDE+2 and the cis-dG-adduct for BPDE+1. The major question is: Does differential repair of the two kinds of DNA adducts account for the differences in their carcinogenicity? The stability of complexes of the Escherichia coli damage recognition protein, UvrA, with undamaged DNA and DNA damaged by uv light, BPDE+1 or BPDE+2 were determined by dissociation reactions. The dissociation rate constants are, respectively, 0.216, 0.144, 0.060, and 0.056 min$\sp{-1}$. The initial rate of UvrABC incision of undamaged DNA, UV-damaged DNA, BPDE+1-modified DNA, and BPDE+2-modified DNA were 4.9 $\times$ 10$\sp{-3}$, 1.9 $\times$ 10$\sp{-2}$, 5.3 $\times$ 10$\sp{-3}$, and 1.2 $\times$ 10$\sp{-2}$ min$\sp{-1}$, respectively. The results suggest that the relative stability of UvrA bound to BPDE+1 modified DNA and BPDE+2 modified DNA does not correlate to their different carcinogenicity, and the efficiency of UvrABC incision depends on the conformation of DNA adducts.