title: MutS switches between two fundamentally distinct clamps during mismatch repair.
abstract: Single-molecule trajectory analysis has suggested DNA repair proteins may carry out a one-dimensional (1D) search on naked DNA encompassing >10,000 nucleotides. Organized cellular DNA (chromatin) presents substantial barriers to such lengthy searches. Using dynamic single-molecule fluorescence resonance energy transfer, we determined that the mismatch repair (MMR) initiation protein MutS forms a transient clamp that scans duplex DNA for mismatched nucleotides by 1D diffusion for 1 s (~700 base pairs) while in continuous rotational contact with the DNA. Mismatch identification provokes ATP binding (3 s) that induces distinctly different MutS sliding clamps with unusual stability on DNA (~600 s), which may be released by adjacent single-stranded DNA (ssDNA). These observations suggest that ATP transforms short-lived MutS lesion scanning clamps into highly stable MMR signaling clamps that are capable of competing with chromatin and recruiting MMR machinery, yet are recycled by ssDNA excision tracts.
authors.affiliation: Department of Physics, Pohang University of Science and Technology, Pohang, Korea.
authors.forename: Cherlhyun
authors.initials: C
authors.lastname: Jeong
authors.forename: Won-Ki
authors.initials: WK
authors.lastname: Cho
authors.forename: Kyung-Mi
authors.initials: KM
authors.lastname: Song
authors.forename: Christopher
authors.initials: C
authors.lastname: Cook
authors.forename: Tae-Young
authors.initials: TY
authors.lastname: Yoon
authors.forename: Changill
authors.initials: C
authors.lastname: Ban
authors.forename: Richard
authors.initials: R
authors.lastname: Fishel
authors.forename: Jong-Bong
authors.initials: JB
authors.lastname: Lee
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D053843:DNA Mismatch Repair; D004269:DNA, Bacterial / Q000235:genetics / Q000378:metabolism*; D004277:DNA, Single-Stranded / Q000235:genetics / Q000378:metabolism; D031541:Fluorescence Resonance Energy Transfer; D008958:Models, Molecular; D051719:MutS DNA Mismatch-Binding Protein / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D013824:Thermus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D004277:DNA, Single-Stranded; D000255:Adenosine Triphosphate; D051719:MutS DNA Mismatch-Binding Protein