ArticleProceedings of the National Academy of Sciences of the United States of America2010
Saccharomyces cerevisiae Msh2-Msh6 DNA binding kinetics reveal a mechanism of targeting sites for DNA mismatch repair.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 26 citations in OpenAlex.
- Mismatch repair disturbs meiotic crossover control in S. cerevisiae.Nucleic acids research · 2025Article
- Recent Advances in Directed Yeast Genome Evolution.Journal of fungi (Basel, Switzerland) · 2022Review
- Melting temperature measurement and mesoscopic evaluation of single, double and triple DNA mismatches.Chemical science · 2020Article
- Mechanisms of glycosylase induced genomic instability.PloS one · 2017Article
- Mismatch binding, ADP-ATP exchange and intramolecular signaling during mismatch repair.DNA repair · 2016Review
- Slow conformational changes in MutS and DNA direct ordered transitions between mismatch search, recognition and signaling of DNA repair.Journal of molecular biology · 2013Article
- Postreplicative mismatch repair.Cold Spring Harbor perspectives in biology · 2013Review
- DnaN clamp zones provide a platform for spatiotemporal coupling of mismatch detection to DNA replication.Molecular microbiology · 2013Article
- Applying 6-methylisoxanthopterin-enhanced fluorescence to examine protein-DNA interactions in the picomolar range.Biochemistry · 2012Article
- Single-molecule multiparameter fluorescence spectroscopy reveals directional MutS binding to mismatched bases in DNA.Nucleic acids research · 2012Article
- Dynamical allosterism in the mechanism of action of DNA mismatch repair protein MutS.Biophysical journal · 2011Article
- Chemical trapping of the dynamic MutS-MutL complex formed in DNA mismatch repair in Escherichia coli.The Journal of biological chemistry · 2011Article
- Application of stopped-flow kinetics methods to investigate the mechanism of action of a DNA repair protein.Journal of visualized experiments : JoVE · 2010Article
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
The DNA mismatch repair system (MMR) identifies replication errors and damaged bases in DNA and functions to preserve genomic integrity. MutS performs the task of locating mismatched base pairs, loops and lesions and initiating MMR, and the fundamental question of how this protein targets specific sites in DNA is unresolved. To address this question, we examined the interactions between Saccharomyces cerevisiae Msh2-Msh6, a eukaryotic MutS homolog, and DNA in real time. The reaction kinetics reveal that Msh2-Msh6 binds a variety of sites at similarly fast rates (k (ON) approximately 10(7) M(-1) s(-1)), and its selectivity manifests in differential dissociation rates; e.g., the protein releases a 2-Aminopurine:T base pair approximately 90-fold faster than a G:T mismatch. On releasing the 2-Ap:T site, Msh2-Msh6 is able to move laterally on DNA to locate a nearby G:T site. The long-lived Msh2-Msh6.G:T complex triggers the next step in MMR--formation of an ATP-bound clamp--more effectively than the short-lived Msh2-Msh6.2-Ap:T complex. Mutation of Glu in the conserved Phe-X-Glu DNA binding motif stabilizes Msh2-Msh6(E339A).2-Ap:T complex, and the mutant can signal 2-Ap:T repair as effectively as wild-type Msh2-Msh6 signals G:T repair. These findings suggest a targeting mechanism whereby Msh2-Msh6 scans DNA, interrogating base pairs by transient contacts and pausing at potential target sites, and the longer the pause the greater the likelihood of MMR.
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