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Recurrent mismatch binding by MutS mobile clamps on DNA localizes repair complexes nearby

Weninger, Keith; Hao, Pengyu; LeBlanc, Sharonda J.; Case, Brandon C.; Elston, Timothy C.; Hingorani, Manju M.; Erie, Dorothy A.


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  <dc:creator>Weninger, Keith</dc:creator>
  <dc:creator>Hao, Pengyu</dc:creator>
  <dc:creator>LeBlanc, Sharonda J.</dc:creator>
  <dc:creator>Case, Brandon C.</dc:creator>
  <dc:creator>Elston, Timothy C.</dc:creator>
  <dc:creator>Hingorani, Manju M.</dc:creator>
  <dc:creator>Erie, Dorothy A.</dc:creator>
  <dc:date>2020-08-11</dc:date>
  <dc:description>DNA mismatch repair (MMR), the guardian of the genome, commences when MutS identifies a mismatch and recruits MutL to nick the error-containing strand, allowing excision and DNA resynthesis. Dominant MMR models posit that after mismatch recognition, ATP converts MutS to a hydrolysis-independent, diffusive mobile clamp that no longer recognizes the mismatch. Little is known about the postrecognition MutS mobile clamp and its interactions with MutL. Two disparate frameworks have been proposed: One in which MutS–MutL complexes remain mobile on the DNA, and one in which MutL stops MutS movement. Here we use single-molecule FRET to follow the postrecognition states of MutS and the impact of MutL on its properties. In contrast to current thinking, we find that after the initial mobile clamp formation event, MutS undergoes frequent cycles of mismatch rebinding and mobile clamp reformation without releasing DNA. Notably, ATP hydrolysis is required to alter the conformation of MutS such that it can recognize the mismatch again instead of bypassing it; thus, ATP hydrolysis licenses the MutS mobile clamp to rebind the mismatch. Moreover, interaction with MutL can both trap MutS at the mismatch en route to mobile clamp formation and stop movement of the mobile clamp on DNA. MutS's frequent rebinding of the mismatch, which increases its residence time in the vicinity of the mismatch, coupled with MutL's ability to trap MutS, should increase the probability that MutS–MutL MMR initiation complexes localize near the mismatch.

 </dc:description>
  <dc:description>This contains single molecule FRET (smFRET) data following the post-recognition state(s) of MutS and the impact of MutL on its properties.
Funding provided by: National Institute of General Medical SciencesCrossref Funder Registry ID: http://dx.doi.org/10.13039/100000054Award Number: GM109832Funding provided by: National Cancer InstituteCrossref Funder Registry ID: http://dx.doi.org/10.13039/100000054Award Number: CA218304Funding provided by: National Institute of General Medical Sciences**Crossref Funder Registry ID: Award Number: GM079480Funding provided by: National Institute of General Medical Sciences*Crossref Funder Registry ID: Award Number: GM114743Funding provided by: National Institute of General Medical Sciences*Crossref Funder Registry ID: Award Number: GM127145Funding provided by: National Institute of General Medical SciencesCrossref Funder Registry ID: http://dx.doi.org/10.13039/100000057Award Number: GM123602Funding provided by: National Institute of General Medical SciencesCrossref Funder Registry ID: http://dx.doi.org/10.13039/100000057Award Number: GM127151Funding provided by: National Institute of General Medical SciencesCrossref Funder Registry ID: http://dx.doi.org/10.13039/100000057Award Number: GM132263Funding provided by: National Institute of General Medical SciencesAward Number: GM123602Funding provided by: National Institute of General Medical SciencesAward Number: GM132263Funding provided by: National Institute of General Medical SciencesAward Number: GM079480Funding provided by: National Institute of General Medical SciencesAward Number: GM114743Funding provided by: National Institute of General Medical SciencesAward Number: GM127145Funding provided by: National Institute of General Medical SciencesAward Number: GM127151</dc:description>
  <dc:description>Single molecule fluorescence resonance energy transfer (FRET) (smFRET) measurments acquired with a total internal reflection fluorescence wide-field microscope detected by an emCCD. Single immobilized particles are detected in movies and .traces files are extracted for each movie that contain the donor and acceptor intensities as a function of time for all identified molecules in a movie. .itx format traces for donor and acceptor for selected traces are also included. Some spreadsheets for counting various populations are also included.

 

 

 </dc:description>
  <dc:identifier>https://zenodo.org/record/3979403</dc:identifier>
  <dc:identifier>10.5061/dryad.612jm641d</dc:identifier>
  <dc:identifier>oai:zenodo.org:3979403</dc:identifier>
  <dc:relation>doi:10.1073/pnas.1918517117</dc:relation>
  <dc:relation>url:https://zenodo.org/communities/dryad</dc:relation>
  <dc:rights>info:eu-repo/semantics/openAccess</dc:rights>
  <dc:rights>https://creativecommons.org/publicdomain/zero/1.0/legalcode</dc:rights>
  <dc:title>Recurrent mismatch binding by MutS mobile clamps on DNA localizes repair complexes nearby</dc:title>
  <dc:type>info:eu-repo/semantics/other</dc:type>
  <dc:type>dataset</dc:type>
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