@article{hao_leblanc_case_elston_hingorani_erie_weninger_2020, title={Recurrent mismatch binding by MutS mobile clamps on DNA localizes repair complexes nearby}, volume={117}, ISSN={["0027-8424"]}, DOI={10.1073/pnas.1918517117}, abstractNote={Significance DNA mismatch repair (MMR) proteins are essential for correcting base incorporation errors that occur during replication, greatly enhancing genomic stability. In all organisms, MutS and MutL homologs initiate MMR repair and are involved in several other DNA transactions, including DNA-damage–induced apoptosis and homologous recombination. Our study reveals that MutS mobile clamps hydrolyze ATP while remaining bound to DNA and frequently revisit the mismatch. We also find that MutL converts MutS mobile clamps into immobile MutS–MutL complexes. These immobile, multimeric complexes present a striking contrast to current MMR initiation models that envision MutS–MutL sliding freely on the DNA, effectively diffusing away from the mismatch. Our results support mechanisms that localize repair complexes to the vicinity of the mismatch.}, number={30}, journal={PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, author={Hao, Pengyu and LeBlanc, Sharonda J. and Case, Brandon C. and Elston, Timothy C. and Hingorani, Manju M. and Erie, Dorothy A. and Weninger, Keith R.}, year={2020}, month={Jul}, pages={17775–17784} }
 @article{leblanc_gauer_hao_case_hingorani_weninger_erie_2018, title={Coordinated protein and DNA conformational changes govern mismatch repair initiation by MutS}, volume={46}, ISSN={["1362-4962"]}, DOI={10.1093/nar/gky865}, abstractNote={MutS homologs identify base-pairing errors made in DNA during replication and initiate their repair. In the presence of adenosine triphosphate, MutS induces DNA bending upon mismatch recognition and subsequently undergoes conformational transitions that promote its interaction with MutL to signal repair. In the absence of MutL, these transitions lead to formation of a MutS mobile clamp that can move along the DNA. Previous single-molecule FRET (smFRET) studies characterized the dynamics of MutS DNA-binding domains during these transitions. Here, we use protein–DNA and DNA–DNA smFRET to monitor DNA conformational changes, and we use kinetic analyses to correlate DNA and protein conformational changes to one another and to the steps on the pathway to mobile clamp formation. The results reveal multiple sequential structural changes in both MutS and DNA, and they suggest that DNA dynamics play a critical role in the formation of the MutS mobile clamp. Taking these findings together with data from our previous studies, we propose a unified model of coordinated MutS and DNA conformational changes wherein initiation of mismatch repair is governed by a balance of DNA bending/unbending energetics and MutS conformational changes coupled to its nucleotide binding properties.}, number={20}, journal={NUCLEIC ACIDS RESEARCH}, author={LeBlanc, Sharonda J. and Gauer, Jacob W. and Hao, Pengyu and Case, Brandon C. and Hingorani, Manju M. and Weninger, Keith R. and Erie, Dorothy A.}, year={2018}, month={Nov}, pages={10782–10795} }
 @misc{leblanc_kulkarni_weninger_2018, title={Single Molecule FRET: A Powerful Tool to Study Intrinsically Disordered Proteins}, volume={8}, ISSN={["2218-273X"]}, DOI={10.3390/biom8040140}, abstractNote={Intrinsically disordered proteins (IDPs) are often modeled using ideas from polymer physics that suggest they smoothly explore all corners of configuration space. Experimental verification of this random, dynamic behavior is difficult as random fluctuations of IDPs cannot be synchronized across an ensemble. Single molecule fluorescence (or Förster) resonance energy transfer (smFRET) is one of the few approaches that are sensitive to transient populations of sub-states within molecular ensembles. In some implementations, smFRET has sufficient time resolution to resolve transitions in IDP behaviors. Here we present experimental issues to consider when applying smFRET to study IDP configuration. We illustrate the power of applying smFRET to IDPs by discussing two cases in the literature of protein systems for which smFRET has successfully reported phosphorylation-induced modification (but not elimination) of the disordered properties that have been connected to impacts on the related biological function. The examples we discuss, PAGE4 and a disordered segment of the GluN2B subunit of the NMDA receptor, illustrate the great potential of smFRET to inform how IDP function can be regulated by controlling the detailed ensemble of disordered states within biological networks.}, number={4}, journal={BIOMOLECULES}, author={LeBlanc, Sharonda J. and Kulkarni, Prakash and Weninger, Keith R.}, year={2018}, month={Dec} }