@article{xu_zhang_pan_mahn_roland_sagui_weninger_2023, title={Frustration Between Preferred States of Complementary Trinucleotide Repeat DNA Hairpins Anticorrelates with Expansion Disease Propensity}, volume={435}, ISSN={["1089-8638"]}, DOI={10.1016/j.jmb.2023.168086}, abstractNote={DNA trinucleotide repeat (TRs) expansion beyond a threshold often results in human neurodegenerative diseases. The mechanisms causing expansions remain unknown, although the tendency of TR ssDNA to self-associate into hairpins that slip along their length is widely presumed related. Here we apply single molecule FRET (smFRET) experiments and molecular dynamics simulations to determine conformational stabilities and slipping dynamics for CAG, CTG, GAC and GTC hairpins. Tetraloops are favored in CAG (89%), CTG (89%) and GTC (69%) while GAC favors triloops. We also determined that TTG interrupts near the loop in the CTG hairpin stabilize the hairpin against slipping. The different loop stabilities have implications for intermediate structures that may form when TR-containing duplex DNA opens. Opposing hairpins in the (CAG) ∙ (CTG) duplex would have matched stability whereas opposing hairpins in a (GAC) ∙ (GTC) duplex would have unmatched stability, introducing frustration in the (GAC) ∙ (GTC) opposing hairpins that could encourage their resolution to duplex DNA more rapidly than in (CAG) ∙ (CTG) structures. Given that the CAG and CTG TR can undergo large, disease-related expansion whereas the GAC and GTC sequences do not, these stability differences can inform and constrain models of expansion mechanisms of TR regions.}, number={10}, journal={JOURNAL OF MOLECULAR BIOLOGY}, author={Xu, Pengning and Zhang, Jiahui and Pan, Feng and Mahn, Chelsea and Roland, Christopher and Sagui, Celeste and Weninger, Keith}, year={2023}, month={May} }
 @article{goetz_barth_bohr_boerner_chen_cordes_erie_gebhardt_hadzic_hamilton_et al._2022, title={A blind benchmark of analysis tools to infer kinetic rate constants from single-molecule FRET trajectories}, volume={13}, ISSN={["2041-1723"]}, DOI={10.1038/s41467-022-33023-3}, abstractNote={Single-molecule FRET (smFRET) is a versatile technique to study the dynamics and function of biomolecules since it makes nanoscale movements detectable as fluorescence signals. The powerful ability to infer quantitative kinetic information from smFRET data is, however, complicated by experimental limitations. Diverse analysis tools have been developed to overcome these hurdles but a systematic comparison is lacking. Here, we report the results of a blind benchmark study assessing eleven analysis tools used to infer kinetic rate constants from smFRET trajectories. We test them against simulated and experimental data containing the most prominent difficulties encountered in analyzing smFRET experiments: different noise levels, varied model complexity, non-equilibrium dynamics, and kinetic heterogeneity. Our results highlight the current strengths and limitations in inferring kinetic information from smFRET trajectories. In addition, we formulate concrete recommendations and identify key targets for future developments, aimed to advance our understanding of biomolecular dynamics through quantitative experiment-derived models.}, number={1}, journal={NATURE COMMUNICATIONS}, author={Goetz, Markus and Barth, Anders and Bohr, Soren S-R and Boerner, Richard and Chen, Jixin and Cordes, Thorben and Erie, Dorothy A. and Gebhardt, Christian and Hadzic, Melodie C. A. S. and Hamilton, George L. and et al.}, year={2022}, month={Sep} }
 @article{fontecha_mahn_bochinski_clarke_2022, title={Tracking the complete degradation lifecycle of poly(ethyl cyanoacrylate): From induced photoluminescence to nitrogen-doped nano-graphene precursor residue}, volume={195}, ISSN={["1873-2321"]}, DOI={10.1016/j.polymdegradstab.2021.109772}, abstractNote={• Superglue (a polymer called poly(ethyl cyanoacrylate)) degrades at moderate temperatures by reverting to a volatile monomer, but also has a side-reaction that forms a carbonaceous by-product. • During thermal degradation, superglue also forms a luminescent by-product. • The photoluminescence observed from heated superglue is depolarized and shifts toward lower energy emission as the thermal degradation progresses. • The final end product of superglue degrading by heating is a non-luminescent graphene-like residue. Poly(ethyl cyanoacrylate) (PECA) is a commercial polymer which degrades easily at temperatures between 150 - 200 °C via an unzipping reaction where volatile monomer is produced. In this report, the complete moderate-temperature degradation lifecycle is delineated, which also includes formation of a carbonaceous by-product where the ester side groups are lost and ring formation between the backbone and cyano side group occurs. Degradation-induced photoluminescence is observed at an intermediate point where the remaining PECA (or re-polymerized oligomers) has sp 3 carbons but sp 2 -carbon-containing clusters of the by-product that will ultimately form aromatic structures are also present. This observation supports the hypothesis that degradation-induced photoluminescence in polymers, which has been observed widely, is connected to the formation of such sp 2 containing clusters, and that this process is relatively independent of the original polymer chemistry, as PECA dominantly degrades through a mechanism distinctly different than the thermo-oxidative cascade associated with many thermoplastic materials. As degradation further advances, a residue of approximately 8% of the original mass is produced which is no longer photoluminescent and can ultimately transform into nitrogen-substituted nano-graphene. Observing the entire lifecycle further solidifies the previously-proposed connection between degradation-induced luminescence in polymers and photoluminescence in hydrogenated amorphous carbon. The low degradation temperature of PECA also provides a bridge between classic polymer degradation and waste-to-graphene strategies that generally involve much more aggressive processing.}, journal={POLYMER DEGRADATION AND STABILITY}, author={Fontecha, Daniela and Mahn, Chelsea and Bochinski, Jason R. and Clarke, Laura I}, year={2022}, month={Jan} }
 @article{kaur_barnes_pan_detwiler_liu_mahn_hall_messenger_you_piehler_et al._2021, title={TIN2 is an architectural protein that facilitates TRF2-mediated trans- and cis-interactions on telomeric DNA}, volume={49}, ISSN={["1362-4962"]}, DOI={10.1093/nar/gkab1142}, abstractNote={The telomere specific shelterin complex, which includes TRF1, TRF2, RAP1, TIN2, TPP1 and POT1, prevents spurious recognition of telomeres as double-strand DNA breaks and regulates telomerase and DNA repair activities at telomeres. TIN2 is a key component of the shelterin complex that directly interacts with TRF1, TRF2 and TPP1. In vivo, the large majority of TRF1 and TRF2 are in complex with TIN2 but without TPP1 and POT1. Since knockdown of TIN2 also removes TRF1 and TRF2 from telomeres, previous cell-based assays only provide information on downstream effects after the loss of TRF1/TRF2 and TIN2. Here, we investigated DNA structures promoted by TRF2-TIN2 using single-molecule imaging platforms, including tracking of compaction of long mouse telomeric DNA using fluorescence imaging, atomic force microscopy (AFM) imaging of protein-DNA structures, and monitoring of DNA-DNA and DNA-RNA bridging using the DNA tightrope assay. These techniques enabled us to uncover previously unknown unique activities of TIN2. TIN2S and TIN2L isoforms facilitate TRF2-mediated telomeric DNA compaction (cis-interactions), dsDNA-dsDNA, dsDNA-ssDNA and dsDNA-ssRNA bridging (trans-interactions). Furthermore, TIN2 facilitates TRF2-mediated T-loop formation. We propose a molecular model in which TIN2 functions as an architectural protein to promote TRF2-mediated trans and cis higher-order nucleic acid structures at telomeres.}, number={22}, journal={NUCLEIC ACIDS RESEARCH}, author={Kaur, Parminder and Barnes, Ryan and Pan, Hai and Detwiler, Ariana C. and Liu, Ming and Mahn, Chelsea and Hall, Jonathan and Messenger, Zach and You, Changjiang and Piehler, Jacob and et al.}, year={2021}, month={Dec}, pages={13000–13018} }