MutS/MutL crystal structure reveals that the MutS sliding clamp loads MutL onto DNA
- Netherlands Cancer Institute, Netherlands
- Justus-Liebig-University, Germany
- Erasmus Medical Center, Netherlands
- MRC Laboratory of Molecular Biology, United Kingdom
Abstract
To avoid mutations in the genome, DNA replication is generally followed by DNA mismatch repair (MMR). MMR starts when a MutS homolog recognizes a mismatch and undergoes an ATP-dependent transformation to an elusive sliding clamp state. How this transient state promotes MutL homolog recruitment and activation of repair is unclear. Here we present a crystal structure of the MutS/MutL complex using a site-specifically crosslinked complex and examine how large conformational changes lead to activation of MutL. The structure captures MutS in the sliding clamp conformation, where tilting of the MutS subunits across each other pushes DNA into a new channel, and reorientation of the connector domain creates an interface for MutL with both MutS subunits. Our work explains how the sliding clamp promotes loading of MutL onto DNA, to activate downstream effectors. We thus elucidate a crucial mechanism that ensures that MMR is initiated only after detection of a DNA mismatch.
Article and author information
Author details
Copyright
© 2015, Groothuizen et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 5,815
- views
-
- 1,196
- downloads
-
- 97
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Citations by DOI
-
- 97
- citations for umbrella DOI https://doi.org/10.7554/eLife.06744
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
MutS/MutL crystal structure reveals that the MutS sliding clamp loads MutL onto DNA
eLife 4:e06744.
https://doi.org/10.7554/eLife.06744
