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Altered DNA dynamics at lesion sites are implicated in how DNA repair proteins pause and identify damage within genomic DNA. We examined DNA dynamics in the context of damage recognition by Rad4 (yeast ortholog of XPC), which recognizes diverse lesions from environmental mutagens and initiates nucleotide excision repair. Previous studies with a cytosine-analog FRET pair placed on either side of 3 base-pair (bp) mismatched sites – recognized specifically by Rad4 in vitro – unveiled severely deformed DNA even without Rad4 (Chakraborty et al. (2018) Nucleic Acid Res. 46: 1240-1255). Here, using laser T-jump, we revealed the timescales of these spontaneous deformations. 3-bp AT-rich nonspecific sites, whether matched or mismatched, exhibited conformational dynamics primarily within the T-jump observation window (~20 µs – <100 ms), albeit with some amplitude in unresolved (<20 µs) kinetics. The amplitudes of the “missing” fast kinetics increased dramatically for mismatched specific sites, which were further distinguished by additional “missing” amplitude in slow (>100 ms) kinetics at elevated temperatures. We posit that the rapid (µs-ms) fluctuations help stall a diffusing protein at AT-rich/damaged sites and that the >100-ms kinetics reflect a propensity for specific DNA to adopt unwound/bent conformations that may resemble Rad4-bound structures. These studies provide compelling evidence for unusual DNA dynamics and deformability that likely govern how Rad4 senses DNA damage. 

When schools and universities across the world transitioned online due to the COVID-19 pandemic, Ed+gineering, a National Science Foundation (NSF) project that partners engineering and education undergraduates to design and deliver engineering lessons to elementary students, also had to shift its hands-on lessons to a virtual format. Through the lens of social cognitive theory (SCT), this study investigates engineering and education students’ experiences during the shift to online instruction to understand how they perceived its influence on their learning. As a result of modifying their lessons for online delivery, students reported learning professional skills, including skills for teaching online and educational technology skills, as well as Science, Technology, Engineering, and Mathematics (STEM) content. Some also lamented missed learning opportunities, like practice presenting face-to-face. Students’ affective responses were often associated with preparing and delivering their lessons. SCT sheds light on how the mid-semester change in their environment, caused by the shift in designing and teaching from face-to-face to online, affected the undergraduate engineering and education students’ personal experiences and affect. Overall, the transition to fully online was effective for students’ perceived learning and teaching of engineering. Though students experienced many challenges developing multimedia content for delivering hands-on lessons online, they reported learning new skills and knowledge and expressed positive affective responses. From the gains reported by undergraduates, we believe that this cross-disciplinary virtual team assignment was a successful strategy for helping undergraduates build competencies in virtual skills. We posit that similar assignment structures and opportunities post-pandemic will also continue to prepare future students for the post-pandemic workplace. 

Abstract Described herein are the first total syntheses of (±)‐dracocephalone A (1) and (±)‐dracocequinones A (4) and B (5). The synthesis was initially envisioned as proceeding through an intramolecular isobenzofuran Diels–Alder reaction, a strategy that eventually evolved into a Lewis acid‐promoted spirocyclization. This highly diastereoselective transformation set the stage fortrans‐decalin formation and a late‐stage Suárez oxidation that produced a [3.2.1] oxabicycle suited for conversion to1. Brønsted acid‐mediated aromatization, followed by a series of carefully choreographed oxidations, allowed for rearrangement to a [2.2.2] oxabicycle poised for conversion to4and5.