MCB9 - DNA Topology and Topoisomerases Lk ≡ integral...

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Unformatted text preview: DNA Topology and Topoisomerases Lk ≡ integral number of times one strand wraps around another Wr ∝ Number of times the DNA duplex wraps around itself Lk = Tw + Wr Tw ∝ N/h (Number of bp divided by DNA pitch) (pitch ≈ 10.5bp/turn) Tw always positive for B-DNA (right handed), strongly constrained by pitch If Wr≈0, Lk≈Tw If Tw is constant, and Lk changes, Wr must change (and vice versa) ∆Lk = ∆Tw + ∆Wr Non-zero values of Wr → supercoiling Wr can be either positive or negative Right handed Left handed Increasing supercoiling Luger et al., Nature, 1997 ∆Lk=-1, topoisomerase Increasing [EtBr] Intercalator Todd et al. J Med. Chem 1999 Chemla et al., Nature 2001 Redinbo et al., Science 1998 II Y III ssDNA Binding DNA Cleavage IV I DNA Release Strand passage Religation Classen et al., PNAS 2003; Dong & Berger Nature 2007 Corbett et al., Nat Struct Mol Biol 2007 1 2 4 3 ADP ...
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