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| Title | The selection process of licensing a DNA mismatch for repair. |
|---|---|
| Journal, issue, pages | Nat Struct Mol Biol, Vol. 28, Issue 4, Page 373-381, Year 2021 |
| Publish date | Apr 5, 2021 |
 Authors | Rafael Fernandez-Leiro / Doreth Bhairosing-Kok / Vladislav Kunetsky / Charlie Laffeber / Herrie H Winterwerp / Flora Groothuizen / Alexander Fish / Joyce H G Lebbink / Peter Friedhoff / Titia K Sixma / Meindert H Lamers /     |
| PubMed Abstract | DNA mismatch repair detects and removes mismatches from DNA by a conserved mechanism, reducing the error rate of DNA replication by 100- to 1,000-fold. In this process, MutS homologs scan DNA, ...DNA mismatch repair detects and removes mismatches from DNA by a conserved mechanism, reducing the error rate of DNA replication by 100- to 1,000-fold. In this process, MutS homologs scan DNA, recognize mismatches and initiate repair. How the MutS homologs selectively license repair of a mismatch among millions of matched base pairs is not understood. Here we present four cryo-EM structures of Escherichia coli MutS that provide snapshots, from scanning homoduplex DNA to mismatch binding and MutL activation via an intermediate state. During scanning, the homoduplex DNA forms a steric block that prevents MutS from transitioning into the MutL-bound clamp state, which can only be overcome through kinking of the DNA at a mismatch. Structural asymmetry in all four structures indicates a division of labor between the two MutS monomers. Together, these structures reveal how a small conformational change from the homoduplex- to heteroduplex-bound MutS acts as a licensing step that triggers a dramatic conformational change that enables MutL binding and initiation of the repair cascade. |
 External links | Nat Struct Mol Biol / PubMed:33820992 |
| Methods | EM (single particle) |
| Resolution | 3.9 - 6.9 Å |
| Structure data | EMDB-11791, PDB-7ai5: EMDB-11792, PDB-7ai6: EMDB-11793, PDB-7ai7: EMDB-11794, PDB-7aib: EMDB-11795, PDB-7aic: |
| Chemicals |  ChemComp-ATP:  ChemComp-ADP:  ChemComp-ANP: |
| Source |
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 Keywords |  DNA BINDING PROTEIN / DNA Mismatch Repair MutS |
