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. Author manuscript; available in PMC: 2011 May 17.
Published in final edited form as: Cell Cycle. 2010 Jun 15;9(12):2317–2329. doi: 10.4161/cc.9.12.11902

Fig. 3. Benzo[c]phenathrenyl ring orientation in duplex DNA influences its ability to inhibit DNA unwinding by the advancing 3’ to 5’ WRN helicase.

Fig. 3

Panel A, View looking into the major groove and normal to the helix axis of the solution structure of the central d(T4-C5-[BPh]A6-C7-T8)-d(A15-G16-T17-G18-A19) segment of Left, the (+)-trans-anti-[BcPh]dA-dT 11-mer duplex, and Right, the (−)-trans-anti-[BcPh]dA-dT 11-mer duplex. The benzo[c]phenanthrenyl moiety, shown in red bonds, is intercalating in the 5’-side direction of the lesion site between d(C5-[BPh]A6)-d(T17-G18) base pairs in the (+)-trans-anti isomer (Left) and in the 3’-side direction between d([BPh]A6-C7-d(G16-T17) base pairs in the (−)-trans-anti isomer (Right). The bonds of the adenine ring are shown in blue. Adapted from a figure that is reproduced by copyright permission from Biochemistry 1995, 34: 1295–1307. Panel B, model depicting effect of trans-opened BcPh dA stereoisomers in the displaced strand on WRN helicase activity that is dependent on their orientation, such that only adducts oriented toward the advancing helicase inhibited WRN unwinding activity. In figure, bold black arrow indicates efficient DNA unwinding past the BcPh lesion (orange polygon). Panel C, Traffic spikes used to control traffic provide a useful analogy for the orientation-specific effects of trans-opened BcPh dA stereoisomers on WRN helicase activity. If the tiger teeth are orientated toward the advancing automobile, they seriously deter further advance past the tire shredders. However, if the tiger teeth are orientated away from the advancing automobile, they allow access. See ref. 67 and text for details.