PMID: 9159121May 27, 1997Paper

Synergy between adjacent zinc fingers in sequence-specific DNA recognition

Proceedings of the National Academy of Sciences of the United States of America
M IsalanA Klug

Abstract

Zif268-like zinc fingers are generally regarded as independent DNA-binding modules that each specify three base pairs in adjacent, but discrete, subsites. However, crystallographic evidence suggests that a contact also can occur from the second helical position of one finger to the subsite of the preceding finger. Here we show for the three-finger DNA-binding domain of the protein Zif268, and a panel of variants, that deleting the putative contact from finger 3 can affect the binding specificity for the 5' base in the adjoining triplet, which forms part of the binding site of finger 2. This finding demonstrates that Zif268-like zinc fingers can specify overlapping 4-bp subsites, and that sequence specificity at the boundary between subsites arises from synergy between adjacent fingers. This has important implications for the design and selection of zinc fingers with novel DNA binding specificities.

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Citations

Dec 16, 2004·Angewandte Chemie·Lei Wang, Peter G Schultz
Feb 19, 2002·Current Opinion in Biotechnology·D J Segal, C F Barbas
Sep 12, 2000·Current Opinion in Structural Biology·Y Choo, M Isalan
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Dec 30, 2011·Nature Methods·Mark Isalan
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Apr 18, 1998·Nature Structural Biology·Y Choo, J W Schwabe
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Feb 16, 2011·Nucleic Acids Research·Kathy N LamTimothy R Hughes
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Mar 8, 2011·Yi chuan = Hereditas·Qiang Zhong, Shu-Hong Zhao
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Jan 23, 2016·Molecular Therapy : the Journal of the American Society of Gene Therapy·Michael T Certo, Richard A Morgan

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