Article abstract

Nature Chemical Biology 4, 51 - 58 (2007)
Published online: 18 November 2007 | doi:10.1038/nchembio.2007.40

Unnatural substrates reveal the importance of 8-oxoguanine for in vivo mismatch repair by MutY

Alison L Livingston1,4, Valerie L O'Shea1,4, Taewoo Kim2, Eric T Kool2 & Sheila S David3

Escherichia coli MutY has an important role in preventing mutations associated with the oxidative lesion 7,8-dihydro-8-oxo-2'-deoxyguanosine (OG) in DNA by excising adenines from OGdotA mismatches as the first step of base excision repair. To determine the importance of specific steps in the base pair recognition and base removal process of MutY, we have evaluated the effects of modifications of the OGdotA substrate on the kinetics of base removal, mismatch affinity and repair to G-C in an E. coli–based assay. Notably, adenine modification was tolerated in the cellular assay, whereas modification of OG resulted in minimal cellular repair. High affinity for the mismatch and efficient base removal required the presence of OG. Taken together, these results suggest that the presence of OG is a critical feature that is necessary for MutY to locate OGdotA mismatches and select the appropriate adenines for excision to initiate repair in vivo before replication.

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  1. Department of Chemistry, University of Utah, 315 South 1400 East, Salt Lake City, Utah 84112, USA.
  2. Department of Chemistry, Stanford University, Stauffer 1, Stanford, California 94305, USA.
  3. Department of Chemistry, University of California, Davis, One Shields Avenue, Davis, California 95616, USA.
  4. These authors contributed equally to this work.

Correspondence to: Sheila S David3 e-mail: david@chem.ucdavis.edu



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