Structure of the endonuclease domain of MutL: unlicensed to cut.

Journal Article (Journal Article)

DNA mismatch repair corrects errors that have escaped polymerase proofreading, increasing replication fidelity 100- to 1000-fold in organisms ranging from bacteria to humans. The MutL protein plays a central role in mismatch repair by coordinating multiple protein-protein interactions that signal strand removal upon mismatch recognition by MutS. Here we report the crystal structure of the endonuclease domain of Bacillus subtilis MutL. The structure is organized in dimerization and regulatory subdomains connected by a helical lever spanning the conserved endonuclease motif. Additional conserved motifs cluster around the lever and define a Zn(2+)-binding site that is critical for MutL function in vivo. The structure unveils a powerful inhibitory mechanism to prevent undesired nicking of newly replicated DNA and allows us to propose a model describing how the interaction with MutS and the processivity clamp could license the endonuclease activity of MutL. The structure also provides a molecular framework to propose and test additional roles of MutL in mismatch repair.

Full Text

Duke Authors

Cited Authors

  • Pillon, MC; Lorenowicz, JJ; Uckelmann, M; Klocko, AD; Mitchell, RR; Chung, YS; Modrich, P; Walker, GC; Simmons, LA; Friedhoff, P; Guarné, A

Published Date

  • July 9, 2010

Published In

Volume / Issue

  • 39 / 1

Start / End Page

  • 145 - 151

PubMed ID

  • 20603082

Pubmed Central ID

  • PMC2933357

Electronic International Standard Serial Number (EISSN)

  • 1097-4164

Digital Object Identifier (DOI)

  • 10.1016/j.molcel.2010.06.027


  • eng

Conference Location

  • United States