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Structural insights into lesion recognition and repair by the bacterial 8-oxoguanine DNA glycosylase MutM

Nature Structural Biology volume 9, pages 544–552 (2002)Cite this article

Abstract

MutM is a bacterial 8-oxoguanine glycosylase responsible for initiating base-excision repair of oxidized guanine residues in DNA. Here we report five different crystal structures of MutM–DNA complexes that represent different steps of the repair reaction cascade catalyzed by the protein and also differ in the identity of the base opposite the lesion (the 'estranged' base). These structures reveal that the MutM active site performs the multiple steps of base-excision and 3′ and 5′ nicking with minimal rearrangement of the DNA backbone.

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Figure 1: Mechanistic scheme for the reaction cascade catalyzed by MutM.
Figure 2: Overall structure of the MutM–DNA complex (rAb·C).
Figure 3: Comparison of active sites from three different stages of catalysis.
Figure 4: Recognition of the estranged base by MutM.

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Acknowledgements

We are grateful to B. Roe and S. Lewis of the OU Advanced Center for Genome Technology for their help with B. stearothermophilus. The entire staff of MacCHESS, especially C. Heaton and B. Miller, provided valuable assistance with data collection and processing. We thank M. Spong for assistance with the crystallization screens, and members of the Verdine, Harrison and Wiley labs for thoughtful discussions. J.C.F is funded by an NSF predoctoral fellowship and an NIH training grant.

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  1. Department of Molecular and Cellular Biology, Harvard University, Cambridge, 02138, Massachusetts, USA

    J. Christopher Fromme & Gregory L. Verdine

  2. Department of Chemistry and Chemical Biology, Harvard University, Cambridge, 02138, Massachusetts, USA

    Gregory L. Verdine

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Correspondence to Gregory L. Verdine.

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Fromme, J., Verdine, G. Structural insights into lesion recognition and repair by the bacterial 8-oxoguanine DNA glycosylase MutM. Nat Struct Mol Biol 9, 544–552 (2002). https://doi.org/10.1038/nsb809

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