title: Atomic force microscopy captures MutS tetramers initiating DNA mismatch repair.
abstract: In spite of extensive research, the mechanism by which MutS initiates DNA mismatch repair (MMR) remains controversial. We use atomic force microscopy (AFM) to capture how MutS orchestrates the first step of E. coli MMR. AFM images captured two types of MutS/DNA complexes: single-site binding and loop binding. In most of the DNA loops imaged, two closely associated MutS dimers formed a tetrameric complex in which one of the MutS dimers was located at or near the mismatch. Surprisingly, in the presence of ATP, one MutS dimer remained at or near the mismatch site and the other, while maintaining contact with the first dimer, relocated on the DNA by reeling in DNA, thereby producing expanding DNA loops. Our results indicate that MutS tetramers composed of two non-equivalent MutS dimers drive E. coli MMR, and these new observations now reconcile the apparent contradictions of previous 'sliding' and 'bending/looping' models of interaction between mismatch and strand signal.
authors.affiliation: School of Chemistry and Chemical Engineering, Southeast University, Jiangsu, PR China. yj@seu.edu.cn
authors.forename: Yong
authors.initials: Y
authors.lastname: Jiang
authors.forename: Piotr E
authors.initials: PE
authors.lastname: Marszalek
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D053843:DNA Mismatch Repair / Q000235:genetics*; D004269:DNA, Bacterial / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure*; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018625:Microscopy, Atomic Force; D051719:MutS DNA Mismatch-Binding Protein / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D055503:Protein Multimerization
chemical_list: D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; D000255:Adenosine Triphosphate; D051719:MutS DNA Mismatch-Binding Protein; C497175:MutS protein, E coli