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Selective Modulation of DNA Polymerase Activity by Fixed-Conformation Nucleoside Analogues


  • This work was supported in part by United States Public Health Service grants K99 GM084460 (R.L.E.), P01 ES05355 (M.E.), R01 ES010375 (F.P.G.), P30 ES000267 (F.P.G., L.J.M., and M.E.), R37 CA087819 (L.J.M.), and the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research.


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Picking a pucker! Fixed-conformation North (N)- and South (S)-methanocarba-2′-deoxyadenosine-triphosphate (MC-dATP) have different effects in DNA strand extension catalyzed by HIV-1 RT and three human Y-family DNA polymerases (pols). All of the polymerases tested preferred the N-oriented furanose geometry, though pol η could insert both pucker mimics. The growth of malignant breast cancer cells overexpressing pol ι was more severely inhibited by N-MC-dATP than that of nonmalignant breast cells.

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