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Science 24 February 2006:
Vol. 311. no. 5764, pp. 1153 - 1157
DOI: 10.1126/science.1120288
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Reports

Structure of a DNA Glycosylase Searching for Lesions

Anirban Banerjee,1 Webster L. Santos,1 Gregory L. Verdine1,2*

DNA glycosylases must interrogate millions of base pairs of undamaged DNA in order to locate and then excise one damaged nucleobase. The nature of this search process remains poorly understood. Here we report the use of disulfide cross-linking (DXL) technology to obtain structures of a bacterial DNA glycosylase, MutM, interrogating undamaged DNA. These structures, solved to 2.0 angstrom resolution, reveal the nature of the search process: The protein inserts a probe residue into the helical stack and severely buckles the target base pair, which remains intrahelical. MutM therefore actively interrogates the intact DNA helix while searching for damage.

1 Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
2 Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.

* To whom correspondence should be addressed. E-mail: gregory_verdine{at}harvard.edu

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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
The Positively Charged Surface of Herpes Simplex Virus UL42 Mediates DNA Binding.
G. Komazin-Meredith, W. L. Santos, D. J. Filman, J. M. Hogle, G. L. Verdine, and D. M. Coen (2008)
J. Biol. Chem. 283, 6154-6161
   Abstract »    Full Text »    PDF »
A continuous hyperchromicity assay to characterize the kinetics and thermodynamics of DNA lesion recognition and base excision.
C. A. S. A. Minetti, D. P. Remeta, and K. J. Breslauer (2008)
PNAS 105, 70-75
   Abstract »    Full Text »    PDF »
Nucleotide flipping by restriction enzymes analyzed by 2-aminopurine steady-state fluorescence.
G. Tamulaitis, M. Zaremba, R. H. Szczepanowski, M. Bochtler, and V. Siksnys (2007)
Nucleic Acids Res. 35, 4792-4799
   Abstract »    Full Text »    PDF »
A rapid reaction analysis of uracil DNA glycosylase indicates an active mechanism of base flipping.
S. R.W. Bellamy, K. Krusong, and G. S. Baldwin (2007)
Nucleic Acids Res. 35, 1478-1487
   Abstract »    Full Text »    PDF »
Insights into finding a mismatch through the structure of a mispaired DNA bound by a rhodium intercalator.
V. C. Pierre, J. T. Kaiser, and J. K. Barton (2007)
PNAS 104, 429-434
   Abstract »    Full Text »    PDF »
NMR structural and kinetic characterization of a homeodomain diffusing and hopping on nonspecific DNA.
J. Iwahara, M. Zweckstetter, and G. M. Clore (2006)
PNAS 103, 15062-15067
   Abstract »    Full Text »    PDF »
A nucleobase lesion remodels the interaction of its normal neighbor in a DNA glycosylase complex.
A. Banerjee and G. L. Verdine (2006)
PNAS 103, 15020-15025
   Abstract »    Full Text »    PDF »
A base-excision DNA-repair protein finds intrahelical lesion bases by fast sliding in contact with DNA.
P. C. Blainey, A. M. van Oijen, A. Banerjee, G. L. Verdine, and X. S. Xie (2006)
PNAS 103, 5752-5757
   Abstract »    Full Text »    PDF »


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