Abstract
DNA-damage recognition in the nucleotide excision repair (NER) cascade is a complex process, operating on a wide variety of damages. UvrB is the central component in prokaryotic NER, directly involved in DNA-damage recognition and guiding the DNA through repair synthesis. We report the first structure of a UvrB–double-stranded DNA complex, providing insights into the mechanism by which UvrB binds DNA, leading to formation of the preincision complex. One DNA strand, containing a 3′ overhang, threads behind a β-hairpin motif of UvrB, indicating that this motif inserts between the strands of the double helix, thereby locking down either the damaged or undamaged strand. The nucleotide directly behind the β-hairpin is flipped out and inserted into a small, highly conserved pocket in UvrB.
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Acknowledgements
This work has been supported by grants to C.K. from the NIH (GM 070873) and from the Pew Scholars Program in the Biomedical Sciences, and in part by the Intramural Research Program of the National Institute of Environmental Health Sciences, NIH (B.V.H.). The National Synchrotron Light Source in Brookhaven is supported by the US Department of Energy and the NIH, and beamline X26C is supported in part by the State University of New York at Stony Brook and its Research Foundation.
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Supplementary information
Supplementary Fig. 1
UvrB Y95A EMSA and incision data (PDF 580 kb)
Supplementary Table 1
Contacts between UvrB and the DNA (PDF 42 kb)
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Truglio, J., Karakas, E., Rhau, B. et al. Structural basis for DNA recognition and processing by UvrB. Nat Struct Mol Biol 13, 360–364 (2006). https://doi.org/10.1038/nsmb1072
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DOI: https://doi.org/10.1038/nsmb1072
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